P-chiral phospholanes and phosphocyclic compounds and their use in asymmetric catalytic reactions

ABSTRACT

Chiral ligands and metal complexes based on such chiral ligands useful in asymmetric catalysis are disclosed. The metal complexes according to the present invention are useful as catalysts in asymmetric reactions, such as, hydrogenation, hydride transfer, allylic alkylation, hydrosilylation, hydroboration, hydrovinylation, hydroformylation, olefin metathesis, hydrocarboxylation, isomerization, cyclopropanation, Diels-Alder reaction, Heck reaction, isomerization, Aldol reaction, Michael addition; epoxidation, kinetic resolution and [m+n] cycloaddition. Processes for the preparation of the ligands are also described.

BACKGROUND OF THE INVENTION

[0001] This application claims priority from U.S. ProvisionalApplication Serial No. 60/336,939, filed Nov. 9, 2001.

[0002] 1. Field of the Invention

[0003] The present invention relates to novel chiral ligands derivedfrom P-chiral phospholanes and P-chiral phosphocyclic compounds andcatalysts for applications in asymmetric catalysis. More particularly,the present invention relates to transition metal complexes of thesechiral phosphine ligands, which are useful as catalysts in asymmetricreactions, such as, hydrogenation, hydride transfer, hydrocarboxylation,hydrosilylation, hydroboration, hydrovinylation, hydroformylation,allylic alkylation, olefin metathesis, isomerization, cyclopropanation,Diels-Alder reaction, Heck reaction, Aldol reaction, Michael addition,epoxidation, kinetic resolution and [m+n] cycloaddition.

[0004] 2. Description of the Prior Art

[0005] Molecular chirality plays an important role in science andtechnology. The biological activities of many pharmaceuticals,fragrances, food additives and agrochemicals are often associated withtheir absolute molecular configuration. A growing demand inpharmaceutical and fine chemical industries is to develop cost-effectiveprocesses for the manufacture of single-enantiomeric products. To meetthis challenge, chemists have explored many approaches for acquiringenantiomerically pure compounds ranging from optical resolution andstructural modification of naturally occurring chiral substances toasymmetric catalysis using synthetic chiral catalysts and enzymes. Amongthese methods, asymmetric catalysis is perhaps the most efficientbecause a small amount of a chiral catalyst can be used to produce alarge quantity of a chiral target molecule [Book, Ojima, I., Ed.Catalytic Asymmetric Synthesis, VCH, New York, 1993 and Noyori, R.Asymmetric Catalysis In Organic Synthesis, John Wiley & Sons, Inc., NewYork, 1994].

[0006] Asymmetric hydrogenation accounts for major part of allasymmetric synthesis on a commercial scale. Some dramatic examples ofindustrial applications of asymmetric synthesis include Monsanto'sL-DOPA synthesis (asymmetric hydrogenation of a dehydroamino acid, 94 %ee, 20,000 turnovers with a Rh-DIPAMP complex) [Knowles, W. S. Acc.Chem. Res. 1983, 16, 106], Takasago's L-menthol synthesis (asymmetricisomerization, 98 % ee, 300,000 turnovers with a Rh-BINAP complex)[Noyori, R.; Takaya, H. Acc. Chem. Res. 1990, 23, 345] and Norvatis'(S)-Metolachlor synthesis (asymmetric hydrogenation of an imine, 80 %ee, 1,000,000 turnovers with an Ir-ferrocenyl phosphine complex)[Spindler, F.; Pugin, B.; Jalett, H. -P., Buser, H. -P.; Pittelkow, U.;Blaser, H, -U., Altanta, 1996; Chem. Ind. (Dekker), 1996, 63 and Tongni,A. Angew. Chem. Int. Ed. Engl. 1996, 356, 14575].

[0007] Invention of chiral ligands for transition metal-catalyzedreactions plays a critical role in asymmetric catalysis. Not only theenantioselectivity depends on the framework of chiral ligands,reactivities can often be altered by changing the steric and electronicstructure of the ligands.

[0008] Since small changes in the ligand can influence the(delta)(delta)G of the rate-determining step, it is very hard to predictwhich ligand can be effective for any particular reaction or substrate.Accordingly, discovery of new chiral ligands sets the foundation ofhighly enantioselective transition metal-catalyzed reactions.

[0009] In recent years, a large number of chiral ligands have beendeveloped for use in asymmetric catalysis reactions. Despite this, onlyfew chiral ligands have been found to be suitable for use in industryfor the production of chiral molecules that require high selectivity.

[0010] One of the earliest P-chiral phosphine ligands is DIPAMP, whichwas developed by Knowles, J. Am. Chem. Soc., 99, 5946 (1977). TheRh(I)-DIPAMP complex has been used in the synthesis of L-DOPA.

[0011] There are continuing efforts from many groups to developstrategies for making P-chiral ligands for asymmetric catalysis,including, for example, the following: I. Ojima, Ed., CatalyticAsymmetric Synthesis, 2^(nd) ed., VCH publishers, Wheinheim, 2000. Jugeand Genet, Tetrahedron Lett., 30, 6357 (1989), who have developed amethod for making P-chiral phosphines. E. J. Corey, J. Am. Chem. Soc.,115, 11000 (1993), who has developed a method for preparing P-chiralphosphines and diphosphines. An enantioselective deprotonation as amethod for the synthesis of P-chiral phosphines has been applied byEvans, J. Am. Chem. Soc., 117, 9075 (1995). Typically, phosphine-borane,phosphine sulfides have been used. Enantioselective deprotonation ofthese compounds and Cu-mediated coupling reactions can produce a numberof diphosphines. A Cu-mediated coupling reaction was reported by Mislow,J. Am. Chem. Soc., 95, 5839 (1973). Formation of phosphine-borane andremoval of borane have been reported by Imamoto, J. Am. Chem. Soc., 112,5244 (1990), Yamago, J. Chem. Soc., Chem. Commun., 2093 (1994) andLivinghouse, Tetrahedron Lett., 35, 9319 (1994). Desulfurization ofphosphine sulfides is reported by Mislow, J. Am. Chem., Soc., 91, 7023(1969). More recently, Imamoto has successfully used these strategies tomake a number of P-chiral phosphines such as BisP*, J. Am. Chem. Soc.,123, 5268 (2001), MiniPhos, J. Org. Chem., 64, 2988 (1999) and othermixed P-chiral ligands, Org. Lett., 3, 373 (2001).

[0012] These ligands have been used effectively in many asymmetricreactions, especially in asymmetric hydrogenation reactions, such asthose described in Adv. Synth. Catal., 343, 118 (2001).

[0013] Some of these ligands are depicted below:

[0014] Despite the wide variation in the substituted groups in the aboveligands, the majority of these ligands are derivatives of the DIPAMPligand. A possible drawback of these ligands is that ligands having aDIPAMP structure are conformationally flexible and, as a result,enantioselectivity is difficult to optimize.

[0015] In contrast to the ligands of the prior art, the presentinvention provides a phospholane and phosphocyclic structure to restrictthe conformational flexibility such that a high enantioselectivity canbe achieved in the transition metal catalysts prepared from theseligands.

[0016] Thus, from a stereochemical point of view, additional stereogeniccenters (e.g. four or more stereogenic centers) are typically created tomake the novel ligands of the present invention substantially moreselective in asymmetric catalytic reactions than, for example, theDIPAMP and BisP* ligands, which have only two stereogenic centers.

SUMMARY OF THE INVENTION

[0017] The present invention provides a chiral ligand represented by thefollowing formula or its enantiomer:

[0018] wherein X is a divalent group selected from (CR⁴R⁵)_(n),(CR⁴R⁵)_(n)-Z-(CR⁴R⁵) n and group represented by the formula:

[0019] wherein each n is independently an integer from 1 to 6; whereineach R⁴ and R⁵ can independently be hydrogen, alkyl, aryl, substitutedalkyl, substituted aryl, hetereoaryl, ferrocenyl, halogen, hydroxy,alkoxy, aryloxy, alkylthio, arylthio and amido; and

[0020] wherein Z can be O, S, —COO—, —CO—, O—(CR⁴R⁵)_(n)—O, CH₂ (C₆H₄),CH₂ (Ar), CH₂(hetereoaryl), alkenyl, CH₂(alkenyl), C₅H₃N, divalent aryl,2,2′-divalent-1,1′-biphenyl, SiR′₂, PR′ and NR⁶ wherein each of R′ andR⁶ can independently be hydrogen, alkyl, substituted alkyl, aryl,substituted aryl, hydroxy, alkoxy, aryloxy, acyl and alkoxycarbonyl;

[0021] wherein R can be alkyl, aryl, substituted alkyl, substitutedaryl, hetereoaryl, ferrocenyl, alkoxy and aryloxy;

[0022] wherein E can be PR′₂, PR′R″, o-substituted pyridine, oxazoline,chiral oxazoline, CH₂(chiral oxazoline), CR′2(chiral oxazoline),CH₂PR′₂, CH₂(o-substituted pyridine), SiR′₃, CR′₂OH and a grouprepresented by the formula:

[0023] wherein Y can be

(CR⁴R⁵)_(m) and (CR⁴R⁵)_(m)-Z-(CR⁴R⁵)_(m);

[0024] wherein each m is independently an integer from 0 to 3; whereineach R⁴ and R⁵ can independently be hydrogen, alkyl, aryl, substitutedalkyl, substituted aryl, hetereoaryl, ferrocenyl, halogen, hydroxy,alkoxy, aryloxy, alkylthio, arylthio and amido; and wherein Z can be O,S, —CO—, —COO—, O—(CR⁴R⁵)_(n)—O, CH₂ (C₆H₄), CH₂ (Ar), CH₂(hetereoaryl),alkenyl, CH₂(alkenyl), C₅H₃N, divalent aryl,2,2′-divalent-1,1′-biphenyl, SiR′₂, PR′ and NR⁶ wherein each of R′ andR⁶ can independently be hydrogen, alkyl, substituted alkyl, aryl,substituted aryl, hydroxy, alkoxy, aryloxy, acyl and alkoxycarbonyl.

[0025] More particularly, the present invention provides a chiral ligandrepresented by the formula and its enantiomer:

[0026] wherein R can be alkyl, aryl, substituted alkyl, substitutedaryl, hetereoaryl, ferrocenyl, alkoxy and aryloxy; and

[0027] wherein n is from 0 to 2.

[0028] The present invention further provides a catalyst prepared by aprocess including:

[0029] contacting a transition metal salt, or a complex thereof, and achiral ligand according to the present invention as described hereinabove.

[0030] The present invention still further provides a process forpreparation of an asymmetric compound including:

[0031] contacting a substrate capable of forming an asymmetric productby an asymmetric reaction and a catalyst prepared by a processincluding:

[0032] contacting a transition metal salt, or a complex thereof, and achiral ligand according to the present invention as described hereinabove.

[0033] The present invention still further provides a process forpreparing (1R, 1R′, 2R, 2R′)-1,1′-di-alkyl-[2,2′]-diphospholanyl-1,1′-disulfide including the steps of:

[0034] asymmetrically deprotonating a 1-alkyl-phospholane-1-sulfide withn-butyllithium/(−)-sparteine in a solvent to produce an anion of the1-alkyl-phospholane-1-sulfide; and

[0035] contacting the anion of the 1-alkyl-phospholane-1-sulfide andCuCl₂ to oxidatively couple the anion of the1-alkyl-phospholane-1-sulfide and produce a reaction mixture includingthe (1R, 1R′, 2R, 2R′)-1,1′-di-alkyl-[2,2′]-diphospholanyl-1,1′-disulfide.

[0036] Further still, the present invention provides a process forpreparing (1S, 1S′, 2R, 2R′)-1,1′-di-alkyl-[2,2′]-diphospholanylincluding the steps of:

[0037] asymmetrically deprotonating a 1-alkyl-phospholane-1-sulfide withn-butyllithium/(−)-sparteine in a solvent to produce an anion of the1-alkyl-phospholane-1-sulfide;

[0038] contacting the anion of the 1-alkyl-phospholane-1-sulfide andCuCl₂ to oxidatively couple the anion of the1-alkyl-phospholane-1-sulfide and produce a reaction mixture including(1R, 1R′, 2R, 2R′)-1,1′-di-alkyl-[2,2′]-diphospholanyl-1,1 ′-disulfide;

[0039] recrystallizing the (1R, 1R′, 2R,2R′)-1,1′-di-alkyl-[2,2′]-diphospholanyl-1,1′-disulfide from thereaction mixture; and

[0040] contacting the (1R, 1R′, 2R,2R′)-1,1′-di-alkyl-[2,2′]-diphospholanyl-1,1′-disulfide andhexachlorodisilane in a solvent to produce (1S, 1S′, 2R,2R′)-1,1′-di-alkyl-[2,2′]-diphospholanyl.

[0041] The presence of additional stereogenic centers (e.g. four or morestereogenic centers) in the novel ligands of the present invention makesthem substantially more selective in asymmetric catalytic reactionsthan, for example, the DIPAMP and BisP* ligands, which have only twostereogenic centers.

DETAILED DESCRIPTION OF THE INVENTION

[0042] The present invention provides novel P-chiral phospholane andphosphocyclic compounds and described their use in asymmetric catalysis.

[0043] Introduction of cyclic structures can restrict the rotation ofsubstituents adjacent to the phosphines and control of orientations ofthese groups around phosphine can lead effective chiral induction forasymmetric reactions. Metal complexes of these phosphines, and relatednone C₂ symmetric ligands are useful for many asymmetric reactions.

[0044] Tunability of ligand chiral environment is crucial for achievinghigh enantioselectivity. The steric and electronic structure of theconformationally rigid cyclic phosphines can be fine-tuned by variationof ring size and substituents.

[0045] Several new chiral phosphines are developed for asymmetriccatalytic reactions. A variety of asymmetric reactions, such as,hydrogenation, hydride transfer, allylic alkylation, hydrosilylation,hydroboration, hydrovinylation, hydroformylation, olefin metathesis,hydrocarboxylation, isomerization, cyclopropanation, Diels-Alderreaction, Heck reaction, isomerization, Aldol reaction, Michaeladdition, epoxidation, kinetic resolution and [m+n] cycloaddition weredeveloped with these chiral ligands systems.

[0046] The ligands of the present invention can be a racemic mixture ofenantiomers. Preferably, the ligand is a non-racemic mixture ofenantiomers, and more preferably, the ligand is one of the enantiomers.Preferably, the ligand has an optical purity of at least 85% ee, andmore preferably, the ligand has an optical purity of at least 95% ee.

[0047] Representative examples of chiral ligands of the currentinvention are shown below. A number of chiral ligands with desiredstructures according to the present invention can be made and used inthe preparation of the catalysts described in the present invention.

[0048] X═(CH₂)_(n), n=1, 2, 3, 4, 5, 6. CH₂OCH₂, CH₂NHCH₂,CH₂CH(R′)CH(R′), CH₂CH (OR′)CH(OR′), CH₂CH(OH)CH(OH), CH₂CH(OCR′₂O)CH,CH₂CH(OalkylO)CH, CH₂CH(OCHR′O)CH, CH₂NR′CH₂, CH₂CH₂N R′CH₂, CH₂CH₂OCH₂,CH₂(C₆H₄), CH₂(Ar), CH₂(hetereoaryl), CH₂(alkenyl), alkyl, substitutedalkyl, aryl, substituted aryl, CH₂(biaryl), CH₂(ferrocene).

[0049] R=alkyl, aryl, substituted alkyl, substituted aryl, hetereoaryl,ferrocene

[0050] E=PR′₂, PR′R″, o-substituted pyridine, oxazoline, chiraloxazoline, CH₂(chiral oxazoline), CR′₂(chiral oxazoline), CH₂PR′₂,CH₂(o-substituted pyridine), SiR′₃, CR′₂OH

[0051] or E=

[0052] then ligands are:

[0053] Y═(CH₂)_(n), n=0, 1, 2, 3, CH₂NHCH₂, CR′₂, CO, SiR′₂, C₅H₃N,C₆H₄, alkyl substituted alkyl, divalent aryl, 2,2′divalent-1,1′biphenyl,substitued aryl, hetereoaryl, ferrocene

[0054] R′=alkyl, aryl, substituted alkyl, aryl, alkylaryl, H.

[0055] In these ligands, the bridge group X for the phosphocycliccompounds are (CH2)n, n=1, 2, 3, 4, 5, 6. CH2OCH2, CH2NHCH2,,CH2CH(R′)CH(R′), CH2CH(OR′)CH(OR′), CH2CH(OH)CH(OH), CH2CH(OCR′2O)CH,CH2CH(OalkylO)CH, CH2CH(OCHR′O)CH, CH2NR′CH2, CH2CH2NR′CH2, CH2CH2OCH2,CH2(C6H4), CH2(Ar), CH2(hetereoaryl), CH2(alkenyl), alkyl, substitutedalkyl, aryl, substituted aryl, CH2(biaryl), CH2(ferrocene). R is alkyl,aryl, substituted alkyl, substituted aryl, hetereoaryl, ferrocene. E isPR′2, PR′R″, o-substituted pyridine, oxazoline, chiral oxazoline,CH2(chiral oxazoline), CR′2(chiral oxazoline), CH2PR′2,CH2(o-substituted pyridine), SiR′3, CR′2OH.

[0056] then ligands are:

[0057] Y can be (CH2)n, n=0, 1, 2, 3, CH2NHCH2, CH2SCH2, CH2PR′CH2,CR′2, CO, SiR′2, C5H3N, C6H4, alkyl, substituted alkyl, divalent aryl,2,2′divalent-1,1′biphenyl, substituted aryl, hetereoaryl, ferrocene.R′=alkyl, aryl, substituted alkyl, aryl, alkylaryl, H.

[0058] In a preferred embodiment, the ligand of the present inventionincludes compounds represented by the formulas wherein:

[0059] X can be (CH₂)_(n) wherein n is from 1 to 6, CH₂OCH₂, CH₂NHCH₂,CH₂CH(R′)CH(R′), CH₂CH(OR′)CH(OR′), CH₂NR′CH₂, CH₂CH(OH)CH(OH),CH₂CH₂NR′CH₂, CH₂CH₂OCH₂ and a group represented by the formula:

[0060] wherein each R⁴ and R⁵ can independently be hydrogen, alkyl,aryl, substituted alkyl and substituted aryl; and wherein:

[0061] Y can be (CH₂)_(n) wherein n is from 0 to 3, CH₂NHCH₂, CH₂SCH₂,CH₂PR′CH₂, CR′2, CO, SiR′₂, C₅H₃N, C₆H₄, alkylene, substituted alkylene,1,2-divalent arylene, 2,2′-divalent-1,1′-biphenyl, substituted aryl,hetereoaryl and ferrocene.

[0062] More particularly, the chiral ligand can be represented by theformula and its enantiomer:

[0063] wherein R can be alkyl, aryl, substituted alkyl, substitutedaryl, hetereoaryl, ferrocenyl, alkoxy and aryloxy; and

[0064] wherein n is from 0 to 2;

[0065] R can be CH₃, Et, iPr, t-Bu, 1-adamantyl, Et₃C, cyclo-C₅H₉,cyclo-C₆H₁₁, phenyl, p-tolyl, 3,5-dimethylphenyl, 3,5-di-t-butyl phenyl,ortho-anisyl and naphthyl.

[0066] Examples of such ligands include a ligand represented by theformula and its enantiomer:

[0067] and a ligand represented by the formula and its enantiomer:

[0068] The ligands according to the present invention can be in the formof a phosphine borane, phosphine sulfide or phosphine oxide.

[0069] Selective examples of specific chiral ligands are listed below toillustrate the new P-chiral phospholanes and P-chiral phosphocycliccompounds (L1 to L35).

[0070] For each ligand, the corresponding enantiomer is alsocontemplated. These compounds can be prepared from correspondingphosphine-boranes, phosphine sulfides and phosphine oxides.

[0071] Since Ir-catalyzed asymmetric hydrogenation is still highlysubstrate-dependent, development of new efficient chiral ligands forIr-catalyzed hydrogenation is a continuing challenge. After developmentof phosphinooxazoline ligands for Ir-catalyzed asymmetric hydrogenation,Pfaltz and others have continued their efforts for the search of newefficient P, N ligands (A. Lightfoot, P. Schnider, A. Pfaltz, Angew.Chem. Int. Ed. 1998, 37, 2897-2899). Various P, N ligands such asTADDOL-phosphite-oxazoline, PyrPHOX, and phosphinite-oxazoline weresubsequently developed by Pfaltz and coworkers (J. Blankenstein, A.Pfaltz, Angew. Chem. Int. Ed. 2001, 40, 4445-4447). Burgess alsoreported JM-Phos and imidazolylidene-oxazoline (D. -R. Hou, J. H.Reibenspies, K. Burgess, J. Org. Chem. 2001, 66, 206-215; M. T. Powell,D. -R. Hou, M. C. Perry, X. Cui, K. Burgess, J. Am. Chem. Soc. 2001,123, 8878-8879).

[0072] In this invention, we also report a new class of chiral P, Nligands, the phospholane-oxazolines, for Ir-catalyzed asymmetrichydrogenation. Excellent enantioselecitivities have been obtained inhydrogenation of methylstilbenes and methylcinammic esters.

[0073] The present invention further provides a catalyst prepared by aprocess including:

[0074] contacting a transition metal salt, or a complex thereof, and achiral ligand according to the present invention as described hereinabove.

[0075] Suitable transition metals for the preparation of the catalystinclude Ag, Pt, Pd, Rh, Ru, Ir, Cu, Ni, Mo, Ti, V, Re and Mn.

[0076] As mentioned above, the catalyst can be prepared by contacting atransition metal salt or its complex and a ligand according to thepresent invention.

[0077] Suitable transition metal salts or complexes include thefollowing:

[0078] AgX; Ag(OTf); Ag(OTf)₂; AgOAc; PtCl₂; H₂PtCl₄; Pd₂(DBA)₃;Pd(OAc)₂; PdCl₂(RCN)₂; (Pd(allyl)Cl)₂; Pd(PR₃)₄; (Rh(NBD)₂)X; (Rh(NBD)Cl)₂; (Rh(COD)Cl)₂; (Rh(COD)₂)X; Rh(acac)(CO)₂;Rh(ethylene)₂(acac); (Rh(ethylene)₂Cl)₂; RhCl(PPh₃)₃; Rh(CO)₂Cl₂;RuHX(L)₂(diphosphine), RuX₂(L)₂ (diphosphine), Ru(arene)X₂(diphosphine),Ru(aryl group)X₂; Ru(RCOO)₂(diphosphine); Ru(methallyl)2(diphosphine);Ru(aryl group)X₂(PPh₃)₃; Ru(COD)(COT); Ru(COD)(COT)X; RuX₂(cymen);Ru(COD)_(n); Ru(aryl group)X₂(diphosphine); RuCl₂(COD); (Ru(COD)₂)X;RuX₂(diphosphine); RuCl₂(═CHR)(PR′₃)₂; Ru(ArH)Cl₂; Ru(COD)(methallyl)₂;(Ir (NBD)₂Cl)₂; (Ir(NBD)₂)X; (Ir(COD)₂Cl)₂; (Ir(COD)₂)X; CuX (NCCH₃)₄;Cu(OTf); Cu(OTf)₂; Cu(Ar)X; CuX; Ni(acac)₂; NiX₂; (Ni(allyl)X)₂;Ni(COD)₂; MoO₂(acac)₂; Ti(OiPr)₄; VO(acac)₂; MeReO₃; MnX₂ and Mn(acac)₂.

[0079] Each R and R′ in these is independently selected from alkyl oraryl; Ar is an aryl group; and X is a counteranion.

[0080] In the above transition metal salts and complexes, L is a solventand the counteranion X can be halogen, BF₄, B(Ar)₄ wherein Ar isfluorophenyl or 3,5-di-trifluoromethyl-1-phenyl, ClO₄, SbF₆, PF₆,CF₃SO₃, RCOO or a mixture thereof.

[0081] In another aspect, the present invention includes a process forpreparation of an asymmetric compound using the catalysts describedabove. The process includes the step of contacting a substrate capableof forming an asymmetric product by an asymmetric reaction and acatalyst according to the present invention prepared by contacting atransition metal salt, or a complex thereof, and a ligand according tothe present invention.

[0082] Suitable asymmetric reactions include asymmetric hydrogenation,hydride transfer, allylic alkylation, hydrosilylation, hydroboration,hydrovinylation, hydroformylation, olefin metathesis,hydrocarboxylation, isomerization, cyclopropanation, Diels-Alderreaction, Heck reaction, isomerization, Aldol reaction, Michaeladdition; epoxidation, kinetic resolution and [m+n] cycloadditionwherein m=3 to 6 and n=2.

[0083] Preferably, the asymmetric reaction is hydrogenation and thesubstrate to be hydrogenated is an ethylenically unsaturated compound,imine, ketone, enamine, enamide, and vinyl ester.

[0084] The present invention still further includes a process forpreparation of an asymmetric compound including:

[0085] contacting a substrate capable of forming an asymmetric productby an asymmetric reaction and a catalyst prepared by a processincluding:

[0086] contacting a transition metal salt, or a complex thereof, and achiral ligand according to the present invention as described hereinabove.

[0087] The present invention still further includes a process forpreparing (1R, 1R′, 2R, 2R′)-1,1′-di-alkyl-[2,2′]-diphospholanyl-1,1′-disulfide including the steps of:

[0088] asymmetrically deprotonating a 1-alkyl-phospholane-1-sulfide withn-butyllithium/(−)-sparteine in a solvent to produce an anion of the1-alkyl-phospholane-1-sulfide; and

[0089] contacting the anion of the 1-alkyl-phospholane-1-sulfide andCuCl₂ to oxidatively couple the anion of the1-alkyl-phospholane-1-sulfide and produce a reaction mixture includingthe (1R, 1R′, 2R,2R′)-1,1′-di-alkyl-[2,2′]-diphospholanyl-1,1′-disulfide.

[0090] Further still, the present invention includes a process forpreparing (1S, 1S′, 2R, 2R′)-1,1′-di-alkyl-[2,2′]-diphospholanyl.

[0091] The process includes the steps of:

[0092] asymmetrically deprotonating a 1-alkyl-phospholane-1-sulfide withn-butyllithium/(−)-sparteine in a solvent to produce an anion of the1-alkyl-phospholane-1-sulfide;

[0093] contacting the anion of the 1-alkyl-phospholane-1-sulfide andCuCl₂ to oxidatively couple the anion of the1-alkyl-phospholane-1-sulfide and produce a reaction mixture comprising(1R, 1R′, 2R, 2R′)-1,1′-di-alkyl-[2,2′]-diphospholanyl-1,1′-disulfide;

[0094] recrystallizing the (1R, 1R′, 2R,2R′)-1,1′-di-alkyl-[2,2′]-diphospholanyl-1,1′-disulfide from thereaction mixture; and

[0095] contacting the (1R, 1R′, 2R,2R′)-1,1′-di-alkyl-[2,2′]-diphospholanyl-1,1′-disulfide andhexachlorodisilane in a solvent to produce (1S, 1S′, 2R,2R′)-1,1′-di-alkyl-[2,2′]-diphospholanyl.

[0096] Preferably, (1S, 1S′, 2R,2R′)-1,1′-di-alkyl-[2,2′]-diphospholanyl is (1S, 1S′, 2R,2R′)-1,1′-di-tert-butyl-[2,2′]-diphospholanyl, which is prepared fromsuitable tert-butyl group containing starting materials.

[0097] Several suitable procedures to prepare the chiral ligandsaccording to the present invention are described herein below.

[0098] (a) Synthesis of TangPhos Using Asymmetric Deprotonation

[0099] (b) Synthesis of TangPhos Through Chiral Separation

[0100] (c) Synthesis of TangPhos Ligands Through Utilization of BackboneChirality

[0101] (d) Synthesis of TangPhos Ligands Through a Chiral Pool Method

[0102] (e) Synthesis of PN Ligands for Asymmetric Catalysis

[0103] (a) nBuLi, Sparteine, CO₂; (b) amino alcohol, EDC, HOBT, DMF,then MsCl; (c) Raney Ni

[0104] General Procedures

[0105] All reactions and manipulations were performed in anitrogen-filled glovebox or using standard Schlenk techniques. THF andtoluene were dried and distilled from sodium-benzophenone ketyl undernitrogen. Methylene chloride was distilled from CaH₂. Methanol wasdistilled from Mg under nitrogen. (R, R)-BDNPB was made a solution of 10mg/ml in toluene before use. Column chromatography was performed usingEM silica gel 60 (230˜400 mesh). ¹H, ¹³C and 31P NMR were recorded onBruker WP-200, AM-300, and AMX-360 spectrometers. Chemical shifts werereported in ppm down field from tetramethylsilane with the solventresonance as the internal standard. Optical rotation was obtained on aPerkin-Elmer 241 polarimeter. MS spectra were recorded on a KRATOS massspectrometer MS 9/50 for LR-EI and HR-EI. GC analysis was carried onHelwett-Packard 6890 gas chromatography using chiral capillary columns.HPLC analysis was carried on Waters™ 600 chromatography.

EXAMPLE 1 Synthesis of TangPhos (1)

[0106] An efficient three-step synthetic of chiral C2 symmetric P-chiralbisphospholane route has been developed.

[0107] Preparation of 1-tert-butyl-phospholane 1-sulfide

[0108] Preparation of BrMgCH₂(CH₂)₂CH₂MgBr. To a dry Schlenk flask heldwith magnesium turning (7.92 g, 0.33 mol) in 300 ml dry THF was addeddropwise 1,4-dibromobutane (23.7 g, 0.11 mol) in 50 mL of THF at roomtemperature. The reaction was very exothermic during the addition. Afterthe addition was complete (within 1 h), the resulting dark solution waskept at r.t. for 2 more hours. The whole solution was used directly forthe following reaction.

[0109] To a solution of phosphorous trichloride (13.7 g, 0.10 mol) inTHF (300 mL) was added dropwise a solution of t-BuMgCl in THF (100 mL,1.0M) at −78° C. The addition was complete within 2 hrs. After themixture was stand at −78° C. for 1 h, a solution of BrMgCH₂(CH)₂CH₂MgBrin THF (made above) was added dropwise. The addition was complete within2 hrs. The mixture was then allowed to warm to r.t over 2 h and stirredovernight.

[0110] At room temperature, to the reaction mixture was added sulfurpowder (4.8 g, 0.15 mol) through one portion. The resulting solution wasfurther stirred at r.t. for 2 h. Water (300 mL) was then added. To theTHF layer was added 500 mL EtOAc. The organic layer was washed withwater (300 mL) followed by brine (300 mL), dried over Na₂SO₄, andconcentrated. The resulting oil was passed through a silica gel columnfollowed by recrystallization to give colorless crystalline product1-tert-butyl-phospholane 1-sulfide 8 g (45% yield).

[0111] Synthesis of (1R, 1R′, 2R,2R′)-1,1′-di-tert-butyl-[2,2′]-diphospholanyl 1,1′-disulfide

[0112] At −78° C., to a solution of (−)-sparteine (7.83 mL, 34 mmol) inether (200 mL) was added n-butyllithium (21.3 mL, 34 mmol, 1.6M inhexane) dropwise. The resulting solution was kept at −78° C. for 30 min.Then at this temperature, to the solution was added dropwise a solutionof 1-tert-butyl-phospholane 1-sulfide (5.0 g, 28.4 mmol in ether (100mL). The addition was complete within 1 hr. The resulting mixture waskept at −78° C. and stirred for 8 more hrs. Then dry CuCl₂ (5.73 g, 42.6mmol) was added into the solution through one portion. The resultingsuspension was vigorously stirred and allowed to warm to r.t. over 4hrs. 150 ml of concentrated ammonia was added. The water layer waswashed twice with EtOAc (2×100 mL). The combined organic phase wasfurther washed in a sequence with 5% ammonia (100 mL), 1 N HCl (100 mL),water (100 mL), and brine (100 mL). After dried over Na₂SO₄, thesolution was concentrated under reduced pressure to give an oily solid,which was subsequently purified by passing a silica gel column to give asolid mixture (4 g) of (1R, 1R′, 2R,2R′)-1,1′-di-tert-butyl-[2,2′]-diphospholanyl 1,1′-disulfide (72% ee,83%) and meso compound (1R, 1R′, 2S,2S′)-1,1′-di-teff-butyl-[2,2′]-diphospholanyl 1,1′-disulfide (17%).

[0113] The mixture was recrystallized from ethyl acetate and ethanol togive 700 mg of pure product (1R, 1R′, 2R,2R′)-1,1′-di-tert-butyl-[2,2′]-diphospholanyl 1,1′-disulfide (ee: >99%according to HPLC, total yield: 14%).

[0114] Synthesis of (1S, 1S′, 2R,2R′)-1,1′-di-tert-butyl-[2,2′]-diphospholanyl TangPhos (1)

[0115] To a solution of (1R, 1R′, 2R,2R′)-1,1′-di-tert-butyl-[2,2′]-diphospholanyl 1,1′-disulfide (440 mg,1.26 mmol) in 25 ml benzene was added hexachlorodisilane (3.25 mL, 5.08g, 18.9 mmol). The mixture was stirred at reflux for 4 h. After thesolution was cooled to r.t., 50 mL of degassed 30% (w/w) NaOH solutionwas carefully added to the reaction mixture with an ice-water bath. Theresulting mixture was then stirred at 60° C. until the aqueous layerbecame clear. The two phases were separated. The water phase was washedtwice with degassed benzene (2×30 mL). The combined benzene was driedover Na₂SO₄ and concentrated.

[0116] The solid residue was re-dissolved in a minimum amount ofdegassed dichloromethane, which was subsequently passed through a basicAl₂O₃ plug (eluent: Et₂O:hexane=1:10) to give pure white product (1) 320mg (88% yield).

EXAMPLE 2 Asymmetric Hydrogenation of Dehydroamino Acids GeneralProcedure for Asymmetric Hydrogenation

[0117] To a solution of [Rh(COD)₂]BF₄ (5.0 mg, 0.012 mmol) in THF (10mL) in a glovebox was added a chiral phosphine ligand (TangPhos 0.15 mLof 0.1 M solution in toluene, 0.015 mmol). After stirring the mixturefor 30 min, the dehydroamino acid (1.2 mmol) was added. Thehydrogenation was performed at rt under 20 psi of hydrogen for 24 h. Thereaction mixture was treated with CH₂N₂, then concentrated in Vacuo. Theresidue was passed through a short silica gel column to remove thecatalyst. The enantiomeric excesses were measured by GC using aChirasil-VAL III FSOT column.

[0118] The absolute configuration of products was determined bycomparing the observed rotation with the reported value. All reactionswent in quantitative yield with no by-products found by GC.

[0119] Asymmetric hydorgenation for making alpha amino acid derivativesusing TangPhos (1) as the ligand is shown in the Table below: AsymmetricHydrogenation of Dehydroamino Acid Derivatives^(a)

Entry Substrate ee^(c) (%) 1 Ar = Ph, R = H >99^(d) 2 Ar = Ph, R =CH3 >99 3 Ar = p-F—Ph, R = H  99^(d) 4 Ar = p-F—Ph, R = CH3 >99 5 Ar =p-MeO—Ph, R = H >99^(d,e) 6 Ar = p-MeO—Ph, R = CH3 >99 7 Ar = m-Br—Ph, R= H >99^(d) 8 Ar = m-Br—Ph, R = CH3 >99 9 Ar = o-Cl—Ph, R = H >99^(d) 10Ar = o-Cl—Ph, R = CH3 >99 11 Ar = 2-thienyl, R = H >99^(d) 12 Ar =2-thienyl, R = CH3 >99 13 Ar = 2-naphthyl, R = H >99^(d) 14 Ar =2-naphthyl, R = CH3 >99 15 Ar = Ph, R = H, N-benzoyl >99^(d) 16 Ar = Ph,R = CH3, N-benzoyl >99

EXAMPLE 3 Asymmetric Synthesis of Beta-Amino Acid Derivatives Synthesisof Starting Material 3-Acetamido-3-Aryl-2-Propenoates and3-Acetamido-3-hetero-Aryl-2-Propenoates

[0120] Typical procedure: The starting material methyl3-acetamido-3-phenyl-2-propenoate can be conveniently synthesized fromcheap acetophenone in three steps according to known literatureprocedure in good yields. The literatures are Zhu, G.; Zhen, Z.; Zhang,X. J. Org. Chem. 1999, 64, 6907-6910; Krapcho, A. P.; Diamanti, J. Org.Synth. 1973, 5, 198-201. ¹H-NMR (CDCl₃, 360 MHz) δ(Z isomer) 2.17 (s,3H), 3.77 (s, 3H), 5.29 (s, 1H), 7.37-7.45 (m, 5H); (E isomer) 2.38 (s,3H), 3.77 (s, 3H), 6.65 (s, 1H), 7.37-7.45 (m, 5H).

[0121] Hydrogenation for Making Beta Amino Acid Derivatives with theRh-TangPhos (1) System

geo ee^(b) entry^(a) R₁ R₂ m.^(c) (%) config. 1 Me Et E 99.5 R 2 Me Et Z97.3 R 3 Me i-Pr E 99.3 R 4 Et Me E 99.6 R 5 n-Pr Et E 99.6 R 6 i-Bu MeE 98.5 R 7 Ph Me E/Z 93.8 S 8 p-F—Ph Me E/Z 95.0 S 9 p-Cl—Ph Me E/Z 92.3S 10 p-Br—Ph Me E/Z 95.1 S 11 p-Me—Ph Me E/Z 94.0 S 12 p-MeO—Ph Me E/Z98.5^(d) S 13 p-BnO—Ph Me E/Z 98.5 S 14 o-Me—Ph Me E/Z 74.3 S 15o-MeO—Ph Me E/Z 83.1 S

[0122] For general synthetic procedures of β-aryl β-acetamidoacrylateesters, see Zhou, Y. -G.; Tang, W.; Wang, W. -B.; Li, W.; Zhang, X. J.Am. Chem. Soc. 2002, 124, 4952-4953. For general synthetic procedure ofβ-alkyl β-acetamidoacrylate esters, see Zhu, G.; Chen, Z.; Zhang, X. J.Org. Chem. 1999, 64, 6907-6910. For analytical data of known substratesand products, please also refer to the two aforementioned papers.

[0123] Methyl 3-Acetamido-3-(4-benzyloxyphenyl)-2-propenoate

[0124] Z/E=9:1; ¹H NMR (360 MHz, CDCl₃) δ(Z isomer) 2.06 (s, 3H), 3.65(s, 3H), 4.98 (s, 2H), 5.18 (s, 1H), 6.86 (d, J=6.8 Hz, 2H), 7.28 (m,7H), 10.46 (s, 1H); (E isomer) 2.27 (s, 3H), 3.65 (s, 3H), 4.98 (s, 2H),6.44 (s, 1H), 6.86 (d, J=6.8 Hz, 2H), 7.28 (m, 7H).

[0125] General Procedure for Asymmetric Hydrogenation of β-alkyl orβ-aryl β-acetamidoacrylic esters

[0126] To a solution of P-acetamidoacrylic ester (0.5 mmol) in 4 mL ofdegassed THF Rh[(TangPhos)nbd]SbF₆ (2.5 μmol) was added in a gloveboxfilled with nitrogen. The whole solution was transferred into anautoclave.

[0127] The autoclave was then purged three times with hydrogen andfilled with hydrogen with 20 psi pressure. The resulting reactor wasstirred at room temperature for 24 hr. After release of the hydrogen,the autoclave was opened and the reaction mixture was evaporated.

[0128] The residue was passed through a short silica gel plug to givehydrogenation product P-amino acid derivatives. A small amount of samplewas subjected to chiral GC or HPLC analysis.

[0129] Methyl 3-acetamido-3-(4-benzyloxyphenyl)-propanoate

[0130] 98.5% ee, [α]²⁵ _(D)=−79.5°; ¹H NMR (300 MHz, CDCl₃) δ2.00 (s,3H), 2.83 (dd, J=15.7, 6.2 Hz, 1H), 2.93 (dd, J=15.6, 6.0 Hz, 1H), 3.63(s, 3H), 5.05 (s, 2H), 5.40 (m, 1H), 6.93 (d, 1H), 6.94 (dd, J=6.7, 2.0Hz, 2H), 7.23 (dd, J=6.8, 1.8 Hz, 2H), 6.72 (m, 5H); ¹³C NMR (75 MHz,CDCl₃) δ23.8, 40.2, 49.5, 52.2, 115.4, 127.9, 128.0, 128.4, 129.0,133.3, 137.3, 158.6, 169.7, 172.1; MS (ESI) m/z 328 (M⁺+1); HRMScalculated for C₁₉H₂₂NO₄ 3281549, found 328.1553. Chiral HPLC conditions((s, s)-whelk-01): solvent hexane:isopropanol(1:1); flow rate 1 mL/min;retention time 8.2 min (R), 13.1 min (S).

EXAMPLE 4 Asymmetric Hydrogenation of Enamides

[0131] Table. Rh-Catalyzed Asymmetric Hydrogenation of α-ArylenamidesUsing TangPhos (1)

Entry Substrate Ar R ee [%]^([b]) 1 Ph H >99 2 m-Me—Ph H >99 3 p-CF₃—PhH >99 4 p-Cy—Ph H >99 5 p-Ph—Ph H 99 6 2-naphthyl H >99 7 Ph CH₃ 98 8p-CF₃—Ph CH₃ 98 9 p-MeO—Ph CH₃ 98 10 2-naphthyl CH₃ 99 11 Ph CH(CH₃)₂ 9812 Ph CH₂Ph 99 13

97

EXAMPLE 5 High Turnovers for Asymmetric Hydrogenation of Enamides UsingRh(TangPhos 1) Catalyst

[0132] Asymmetric hydrogenation with [Rh(NBD)TangPhos(1)]⁺SbF₆ ⁻ as thecatalyst:

[0133] Procedure for Hydrogenation of α-dehydro Amino Acid

[0134] To a solution of methyl a-(acetylamino)-2-phenylacrylate (2.19 g,10 mmol) in 20 mL of degassed methanol in glovebox was added[Rh(nbd)(1)]SbF₆(1 ml of 0.001M solution in methanol, 0.001 mmol). Thehydrogenation was performed at room temperature under 40 psi of H₂ for 8h. After carefully releasing the hydrogen, the reaction mixture waspassed through a short silica gel column to remove the catalyst. Theenantiomeric excesses of (R)-methyl 2-acetylamino-3-phenylpropionatewere measured by chiral GC directly. (Conversion: 100%, ee: 99.8%, TON:10,000)

EXAMPLE 6 Asymmetric Hydrogenation of Itaconic Acid Derivatives withRh(TangPhos (1) Catalyst

[0135]

entry R₁ R₂ ^([b]) ee (%)^([c]) 1 H H 99 2 CH₃ CH(CH₃)₂ 96 3 CH₃ Ph 93 4CH₃ p-MeO—Ph 97 5 CH₃ p-Me—Ph 97 6 CH₃ p-Cl—Ph >99 7 CH₃ m-Cl—Ph 99 8CH₃ 1-naphthyl 99 9 CH₃ 2-naphthyl 99

EXAMPLE 7 Asymmetric Hydrogenation of Arylenol Acetates with the[Rh(TangPhos (1)]Catalyst

[0136]

entry Ar ee (%)^([b]) 1 2-naphthyl 97 2 Ph 96 3 p-F—Ph 92 4 p-Cl—Ph 97 52-furyl 93 6 p-NO₂—Ph 99

EXAMPLE 8 Synthesis of Chiral PN ligands for Asymmetric Catalysis

[0137] Since Ir-catalyzed asymmetric hydrogenation is still highlysubstrate-dependent, development of new efficient chiral ligands forIr-catalyzed hydrogenation is a continuing challenge. A new class ofchiral P, N ligands, the phospholane-oxazolines have been developed asfollows:

[0138] At −78° C., to a solution of (−)-sparteine (14.4 mL, 62.5 mmol)in ether (100 mL) was added dropwise n-BuLi (1.6M in hexane, 39 mL, 62.5mmol). The mixture was stirred at −78° C. for 30 min. A solution of 2(10 g, 56.8 mmol) in ether (150 mL) was added dropwise. The addition wascomplete in 1 h. The resulting reaction mixture was allowed to warm tort and stirred overnight. The mixture was re-cooled to −78° C. Throughthe suspension was bubbled CO₂ for 2 h. Then it was quenched with theaddition of 1 N HCl (200 mL) followed by EtOAc (200 mL). The organiclayer was washed sequentially with 1 N HCl (200 mL), H₂O (200 mL), andbrine (100 mL). The solution was dried over Na₂SO₄ and evaporated. Theresidue was treated with 2 N NaOH solution (300 mL). The resulting clearsolution was neutralized by the addition of 2 N HCl. The precipitate wascollected through vacuum filtration to give the product (8.0 g, 72% ee,64% yield). The ee was determined by converting the product into itscorresponding methyl ester by treatment with TMSCHN₂ in THF/CH₃OHsolution (HPLC conditions for the methyl ester: Chiralpak AD column;hex:ipr=95:5; 8.8 min, 11.3 min.) A sample of product (7.5 g) wasrecrystallized twice from ethanol to give 4.5 g of enantiomerically pureproduct 3 (>99.9% ee, 40% total yield).

[0139] 3: [α]_(D) ²⁰=16.9°(c=0.9, CHCl₃); ¹H NMR (360 MHz, CDCl₃) δ1.35(d, ³J_(HP)=17.0 Hz, 9H), 1.71 (m, 1H), 2.18 (m, 3H), 2.47 (m, 2H), 3.34(m, 1H); ¹³C NMR (90 MHz, CD₃OD) δ25.4 (d, ²J_(CP)=1.7 Hz), 26.0 (d,²J_(CP)=2.2 Hz), 31.3 (d, ²J_(CP)=7.3 Hz), 32.8 (d, J_(CP)=48.8 Hz),36.1 (d, J_(CP)=44.1 Hz), 46.4 (d, J_(CP)=36.0), 172.9; ³¹P NMR (145MHz, CD₃OD) δ89.3 (s); APCI MS 121 (M⁺+H); HRMS calculated for C₉H₁₈PSO₂221.0765, found 221.0762.

[0140] The methyl ester of 3: [α]D²⁰=42.6°(C=1, CHCl₃); ¹H NMR (360 MHz,CDCl₃) δ1.21 (d, ³J_(HP)=16.8 Hz, 9H), 1.69 (m, 1H), 1.92 (m, 2H), 2.30(m, 3H), 3.23 (m, 1H), 3.66 (s, 3H); ¹³C NMR (90 MHz, CDCl₃) δ25.2 (d,2.7 Hz), 25.4 (d, ²J_(CP)=1.8 Hz), 29.9 (d, ²J_(JP)=7.4 Hz), 31.7 (d,J_(CP)=47.9 Hz), 35.3 (d, J_(JP)=43.5 Hz), 45.4 (d, J_(CP)=35.5 Hz),52.7, 170.0; ³¹P NMR (145 MHz, CDCl₃) δ87.8; APCI MS 235 (M⁺+H); HRMScalculated for C₁₀H₂₀PSO₂ 235.0922 found 235.0909.

[0141] A mixture of 3 (2.27 mmol), EDC.HCl (1.3 g, 6.82 mmol), HOBT.H₂O(0.52 g, 3.41 mmol), chiral amino alcohol (3.41 mmol), triethylamine(1.9 mL, 13.6 mmol) in 10 mL of DMF was stirred at 70° C. overnight. Tothe cooled mixture was added 30 mL of 2 N HCl solution. The resultingmixture was then extracted with ethyl acetate. The organic layer waswashed with water and brine, dried over Na₂SO₄. After removal of thesolvent, the residue was purified by column chromatography to givecondensation product in 70-80% yield.

[0142] To a mixture of condensation product (1.67 mmol),diisopropylethylamine (1.98 mL, 6.68 mmol) and triethylamine (1.38 mL,16.7 mmol) in 10 mL of CH₂Cl₂ was added 258 μL (3.34 mmol) ofmethanesulfonylchloride at 0° C. After addition, the resulting mixturewas allowed to warm to room temperature and stirred overnight. Thesolvent was removed. The residue was redissolved in ethyl acetate,washed with water and brine, and dried over Na₂SO₄. After removal ofsolvent, the crude product was purified by column chromatography to givepure 4a-f in 70-80% yield.

[0143] 4a: [α]²⁰ _(D)=−75.1°(c=0.9, CHCl₃), ¹H NMR (360 MHz, CDCl₃)δ0.81 (d, 6.8 Hz, 3H), 0.89 (d, 6.8 Hz, 3H), 1.24 (d, ³J_(HP)=16.5 Hz,9H), 1.58 (m, 1H), 1.71 (m, 1H), 1.90 (m, 1H), 2.11 (m, 2H), 2.37 (m,2H), 3.19 (m, 1H), 3.86 (m, 1H), 3.94 (t, 7.9 Hz, 1H), 4.21 (t, 8.1 Hz,1H); ¹³C NMR (90 MHz, CDCl₃) δ18.7, 19.4, 25.4 (m), 30.6 (d, ²J_(CP)=7.9Hz), 31.8 (d, J_(CP)=47.5 Hz), 32.0, 33.1, 35.2 (d, J_(CP)=43.4 Hz),38.8 (d, J_(CP)=39.5 Hz), 70.6, 72.4, 163.9; ³¹P NMR (145 MHz, CDCl₃)δ88.0; APCI MS 288 (M⁺+H); HRMS calculated for C₁₄H₂₇NOPS 288.1551 found288.1549.

[0144] 4b: [α]²⁰ _(D)=−75.9°(c=0.9, CHCl₃), ¹H NMR (360 MHz, CDCl₃)δ0.83 (s, 9H), 1.25 (d, ³J_(HP)=16.4 Hz, 9H), 1.56 (m, 1H), 1.87 (m,1H), 2.14 (m, 2H), 2.38 (m, 2H), 3.21 (m, 1H), 3.83 (m, 1H), 4.01 (t,8.4 Hz, 1H), 4.16 (t, 8.5 Hz, 1H); ¹³C NMR (90 MHz, CDCl₃) δ25.6 (d,²J_(CP)=1.6 Hz), 26.5, 30.6 (d, ²J^(CP)=7.9 Hz), 31.9 (d, J_(CP)=47.2Hz), 32.0, 33.8, 35.3 (d, J_(CP)=43.6 Hz), 38.9 (d, J_(CP)=40.0 Hz),69.1, 75.9, 163.9; ³¹P NMR (145 MHz, CDCl₃) δ87.3; ESI MS 302 (M⁺+H);HRMS calculated for C₁₅H₂₉NOPS 302.1707 found 302.1716.

[0145] 4c: [α]²⁰ _(D)=−98.9°(c=1, CHCl₃), ¹H NMR (360 MHz, CDCl₃) δ1.24(d, ³J_(HP)=16.6 Hz, 9H), 1.58 (m, 1H), 1.91 (m, 1H), 2.16 (m, 2H), 2.39(m, 2H), 3.28 (m, 2H), 3.19 (t, 8.3 Hz, 1H), 4.58 (t, 8.3 Hz, 1H), 5.14(m, 1H), 7.19 (m, 5H); ¹³C NMR (90 MHz, CDCl₃) δ25.0 (d, ²J_(CP)=1.1Hz), 30.2 (d, ²J_(CP)=7.7 Hz), 31.3 (d, J_(CP)=47.3 Hz), 31.5, 34.8 (d,J_(CP)=43.4 Hz), 38.6 (d, J_(CP)=39.2 Hz), 69.6, 74.9, 127.3 (m), 142.3,165.2 (d, ²J_(CP)=4.6 Hz); ³¹P NMR (145 MHz, CDCl₃) δ88.8; APCI MS 322(M⁺+H); HRMS calculated for C₁₇H₂₅NOPS 322.1395 found 322.1409.

[0146] 4d: [α]²⁰ _(D)=−54.2°(c=1, CHCl₃), ¹H NMR (360 MHz, CDCl₃) δ1.17(d, ³J_(HP)=16.5 Hz, 9H), 1.52 (m, 1H), 1.84 (m, 1H), 2.07 (m, 2H), 2.32(m, 2H), 2.58 (dd, 8.2 Hz, 13.6 Hz, 1H), 2.98 (dd, 5.5 Hz, 13.6 Hz,1H),3.06 (dd, 9.6 Hz, 17.3 Hz, 1H), 3.88 (t, 7.3 Hz, 1H), 4.09 (t, 8.5 Hz),4.3 (m, 1H), 7.13 (m, 5H); ¹³C NMR (90 MHz, CDCl₃) δ24.4, 24.6 (d,²J_(CP)=1.2 Hz), 29.8 (d, ²J_(CP)=8.0 Hz), 30.9 (d, J_(CP)=47.4 Hz),34.3 (d, J_(CP)=43.4 Hz), 37.8 (d, J_(CP)=39.1 Hz), 41.5, 66.8, 71.3,125.8, 127.9, 128.8 (m), 163.7 (d, ²J_(CP)=4.7 Hz); ³¹P NMR (145 MHz,CDCl₃) δ88.5; APCI MS 336 (M⁺+H); HRMS calculated for C₁₈H₂₇NOPS336.1551 found 336.1542.

[0147] 4e: [α]²⁰ _(D)=−83.9°(c=1, CHCl₃), ¹H NMR (360 MHz, CDCl₃) δ0.67(t, 6.4 Hz, 6H), 1.04 (d, ³J_(HP)=16.4 Hz, 9H), 1.43 (m, 3H), 1.67 (m,1H), 1.94 (m, 2H), 2.19 (m, 2H), 3.00 (m, 1H), 3.60 (t, 7.4 Hz, 1H),3.91 (m, 1H), 4.08 (m, 8.5 Hz, 1H); ¹³C NMR (90 MHz, CDCl₃) δ22.3, 22.5,24.4, 24.6, 24.9, 29.8 (d, ²J_(CP)=7.9 Hz), 30.9 (d, J_(CP)=47.4 Hz),31.4 Hz, 34.3 (d, J_(CP)=43.4 Hz), 37.9 (d, J_(CP)=39.4 Hz), 45.3, 64.1,72.6, 162.9 (d, ²J_(CP)=4.6 Hz); ³¹P NMR (145 MHz, CDCl₃) δ88.0; ESI MS302 (M⁺+H); HRMS calculated for C₁₅H₂₈NOPS 302.1708 found 302.1715.

[0148] 4f: [α]²⁰ _(D)=+28.6°(c=0.9, CHCl₃), ¹H NMR (360 MHz, CDCl₃)δ0.82 (d, 6.7 Hz, 3H), 0.94 (d, 6.7 Hz, 3H), 0.95 (d, J_(HP)=16.4 Hz,9H), 1.58 (m, 1H), 1.75 (m, 1H), 1.89 (m, 1H), 2.13 (m, 2H), 2.39 (m,2H), 3.11 (m, 1H), 3.81 (m, 1H), 3.95 (t, 8.2 Hz, 1H), 4.20 (t, 8.2 Hz);¹³C NMR (90 MHz, CDCl₃) δ18.6, 20.0, 25.2, 25.4 (d, ²J_(CP)=1.4 Hz),30.7 (d, ²J_(CP)=7.8 Hz), 32.8 (d, J_(CP)=47.6 Hz), 32.0, 33.2, 35.1 (d,J_(CP)=43.6 Hz), 38.7 (d, J_(CP)=39.8 Hz), 70.6, 72.8, 163.7 (d,²J_(CP)=4.5 Hz); ³¹P NMR (145 MHz, CDCl₃) δ87.9; ESI MS 288 (M⁺+H); HRMScalculated for C₁₄H₂₇NOPS 288.1551 found 288.1545.

[0149] General procedure

[0150] To a N₂-flushed Schlenk flask was loaded 5.0 g of Raney Ni 2800slurry. The Raney Ni was washed sequentially with methanol (10 mL×3),ether (10 mL×3), and dried degassed CH₃CN (10 mL×3). To this flask wasthen transferred a solution of 4a-f (1.5 mmol) in CH₃CN (20 mL) viacannula. The resulting mixture was stirred under N₂ for 2 d. The mixturewas then filtered under N₂. The Raney Ni solid was washed with CH₃CN (10mL×5). The combined CH₃CN with filtrate was evaporated under N₂ to givean oily residue. The residue was passed through an Al₂O₃ (basic) plugunder N₂ to give pure oily product 5a-f (80-95%).

[0151] 5a: ¹H NMR (400 MHz, CD₂Cl₂) δ0.88 (d, 6.8 Hz, 3H), 0.94 (d, 6.8Hz, 6.8 Hz), 1.08 (d, ³J_(HP)=11.9 Hz, 9H), 1.72 (m, 4H), 2.01 (b, 3H),2.81 (b, 1H), 3.85 (b, 1H), 3.95 (t, 7.6 Hz, 1H), 4.20 (t, 7.6 Hz, 1H);¹³C NMR (100 MHz, CD₂Cl₂) δ18.3, 18.8, 23.3 (d, ²J_(CP)=17.5 Hz), 27.6(d, ²J_(CP)=14.5 Hz), 29.0, 29.1 (d, J_(CP)=18.4 Hz), 33.2 (d,J_(CP)=19.9 Hz), 36.9 (d, J_(CP)=20.2 Hz), 70.2, 72.4, 169.1 (d,²J_(CP)=15.9 Hz); ³¹P NMR (145 MHz, CD₂Cl₂) δ26.0; ESI MS 256 (M⁺+H);HRMS calculated for C₁₄H₂₇NOP 256.1830 found 256.1820.

[0152] 5b: ¹H NMR (360 MHz, CDCl₃) δ0.71 (s, 9H), 0.90 (d, ³J_(HP)=11.9Hz, 9H), 1.56 (m, 3H), 1.83 (m, 3H), 2.73 (b, 1H), 3.65 (m), 3.92 (t,7.6 Hz, 1H), 3.99 (t, 9.3 Hz, 1H); ¹³C NMR (90 MHz, CDCl₃) δ21.9 (d,²J_(CP)=17.6 Hz), 24.8, 26.4 (d, ²J_(CP)=14.2 Hz), 27.7 (d, 2.84 Hz),28.9 (d, J_(CP)=18.0 Hz), 32.4 (d, J_(CP)=70.0 Hz), 35.8 (d, J_(CP)=19.8Hz), 67.7, 74.4, 168.9 (d,, ²J_(CP)=15.9 Hz); ³¹P NMR (145 MHz, CDCl₃)δ25.2; ESI MS 270 (M⁺+H); HRMS calculated for C₁₅H₂₉NOP 270.1987 found270.1972.

[0153] 5c: ¹H NMR (360 MHz, CD₂Cl₂) δ0.98 (d, ³J_(HP)=12.0 Hz, 9H), 1.66(m, 3H), 1.92 (m, 3H), 2.80 (m, 1H), 3.91 (t, 7.9 Hz, 1H), 4.46 (dd, 8.3Hz, 10.0 Hz, 1H), 5.01 (m, 1H), 7.17 (m, 5H); ¹³C NMR (90 MHz, CD₂Cl₂)δ23.5 (d, ²J_(CP)=17.6 Hz), 27.9 (d, ²J_(CP)=14.4 Hz), 29.2 (d,²J_(CP)=2.1 Hz), 29.4 (d, J_(CP)=18.7 Hz), 33.4, 37.1 (d, J_(CP)=20.1Hz), 70.1, 75.3, 127.0-129.1 (m), 144.0, 172.0 (d, ²J_(CP)=15.8 Hz); ³¹PNMR (145 MHz, CD₂Cl₂) δ27.4; ESI MS 290 (M⁺+H); HRMS calculated forC₁₇H₂₄NOP 290.1674 found 290.1663.

[0154] 5d: ¹H NMR (360 MHz, CD₂Cl₂) δ1.06 (d, ³J_(HP)=11.9 Hz, 9H), 1.74(m, 3H), 2.01 (m, 3H), 2.67 (dd, 7.5 Hz, 13.6 Hz, 1H), 2.74 (m, 1H),2.96 (dd, 6.1 Hz, 13.6 Hz, 1H), 3.92 (dd, 7.0 Hz, 8.2 Hz, 1H), 4.17 (t,9.0 Hz, 1H), 4.30 (m, 1H), 7.28 (m, 5H); ¹³C NMR (90 MHz, CD₂Cl₂) δ23.4(d, J_(CP)=17.9 Hz), 27.8 (d, ²J_(CP)=14.4 Hz), 29.1 (d, ²J_(CP)=2.2Hz), 29.3 (d, J_(CP)=18.7 Hz), 33.4 (d, ²J_(CP)=1.2 Hz), 37.1 (d,J_(CP)=20.0 Hz), 42.5, 68.0, 72.2, 126.8, 128.9, 130.0, 139.2, 170.9 (d,²J_(CP)=15.8 Hz); ³¹P NMR (145 MHz, CD₂Cl₂) δ26.7; ESI MS 304 (M⁺+H);HRMS calculated for C₁₈H₂₇NOP 304.1830 found 304.1836.

[0155] 5e: ¹H NMR (360 MHz, CD₂Cl₂) δ0.86 (d, 4.3 Hz, 3H), 0.92 (d, 4.3Hz, 3H), 1.03 (d, ³J_(HP)=11.9 Hz, 9H), 1.25 (m, 1H), 1.49 (m, 1H), 1.73(m, 4H), 1.95 (m, 3H), 2.74 (m, 1H), 3.75 (t, 7.7 Hz, 1H), 4.03 (m, 1H),4.25 (dd, 8.0 Hz, 9.1 Hz, 1H); ¹³C NMR (90 MHz, CD₂Cl₂) δ23.1, 23.3 (d,²J_(CP)=17.7 Hz), 26.0, 27.8 (d, ²J_(CP)=14.4 Hz), 29.1 (d, ²J_(CP)=2.4Hz), 29.2 (d J_(CP)=18.7 Hz), 33.3 (d, 1.6 Hz), 37.1 (d, J_(CP)=19.9Hz), 46.3, 65.2, 73.4, 169.9 (d, ²J_(CP)=15.8 Hz); ³¹P NMR (145 MHz,CD₂Cl₂) δ26.1; ESI MS 270 (M⁺+H); HRMS calculated for C₁₅H₂₈NOP 270.1987found 270.2042.

[0156] 5f: ¹H NMR (360 MHz, CDCl₃) δ0.73 (d, 6.8 Hz, 3H), 0.80 (d, 6.8Hz, 3H), 0.93 (d, ³J_(HP)=12.0 Hz, 9H), 1.49 (m, 1H), 1.66 (m, 3H), 1.89(m, 3H), 2.66 (m, 1H), 3.76 (m, 1H), 3.84 (t, 7.6 Hz, 1H), 4.07 (t, 8.8Hz, 1H); ¹³C NMR (90 MHz, CDCl₃) δ16.6, 17.9, 21.8 (d, ²J_(CP)=17.4 Hz),26.5 (d, ²J_(CP)=14.3 Hz), 27.5 (d, ²J_(CP)=2.4 Hz), 27.8 (d,J_(CP)=18.0 Hz), 31.3, 31.9 (d, 1.1 Hz), 35.5 (d, J_(CP)=19.8 Hz), 68.5,70.6, 169.0 (d, ²J_(CP)=15.5 Hz); ³¹P NMR (145 MHz, CDCl₃) δ25.9; ESI MS256 (M⁺+H); HRMS calculated for C₁₄H₂₇NOP 256.1830 found 256.1805.

EXAMPLE 9 Preparation of Ir—PN Compounds

[0157]

[0158] General Procedure

[0159] To a Schlenk tube was added 5a-f (0.346 mmol), [Ir(COD)Cl]₂ (116mg, 0.173 mmol), and dried degassed CH₂Cl₂ (4 mL). The deep red mixturewas heated under N₂ to reflux for 1 h, until in situ ³¹P NMR indicatedthat the starting material was consumed. After the reaction mixture wascooled to rt, Na[BARF] (453 mg, 0.519 mmol) was added followed bydegassed H₂O (5 mL), and the resulting two-phase mixture was stirredvigorously for 30 min. The two layers were separated, and the waterlayer was further washed with CH₂Cl₂. The combined CH₂Cl₂ solution wasevaporated to give a brown residue, which was subsequently passedthrough an Al₂O₃ plug (eluent: hexane: CH₂Cl₂=1:2) to give pure orangeproduct 6a-f in 50-70% yield.

[0160] 6a: ¹H NMR (360 MHz, CD₂Cl₂) δ0.74 (d, 6.8 Hz, 3H), 0.91 (d, 7.0Hz, 3H), 1.17 (d, ³J_(HP)=15.4 Hz, 9H), 1.58 (m, 2H), 1.83-2.40 (m,13H), 3.09 (m, 1H), 4.13 (m, 3H), 4.51 (t, 9.4 Hz, 1H), 4.65 (dd, 3.8Hz, 9.4 Hz, 1H), 4.94 (m, 2H), 7.59 (s, 4H), 7.73 (s, 8H); ¹³C NMR (90MHz, CD₂Cl₂) δ14.0, 19.0, 24.0 (d, ²J_(CP)=25.6 Hz), 27.1 (d,²J_(CP)=3.5Hz), 27.8, 30.1 (d, 1.9 Hz), 31.1, 32.2 (d, 1.9 Hz), 32.5 (d,J_(CP)=23.4 Hz), 33.9 (d, 2.1 Hz), 36.2 (d, 3.7 Hz), 37.8 (d,J_(CP)=30.0 Hz), 60.6, 63.1, 70.0, 73.0, 90.3 (d, 11.8 Hz), 93.5 (d,10.9 Hz), 118.0 (t), 120.7, 123.7, 126.7, 129.3 (dd, 28.4 Hz, 58.6 Hz),135.4 (t, 92.9 Hz), 162.3 (q, 49.6 Hz), 190.1 (d, ²J_(CP)=19.7 Hz); ³¹PNMR (145 MHz, CD₂Cl₂) δ51.9; ESI+MS: 556 (cation+1); ESI-MS: 863(anion); HRMS calculated for IrC₂₂H₃₉NOP 556.2320 found 556.2318; HRMScalculated for C₃₂H₁₂F₂₄B 863.0649 found 863.0650.

[0161] 6b: ¹H NMR (360 MHz, CD₂Cl₂) δ0.88 (s, 9H), 1.15 (d, ³J_(HP)=15.4Hz, 9H), 1.43 (b, 2H), 1.60-2.40 (m, 11H), 2.87 (d, 7.6 Hz, 1H), 3.55(m, 1H), 3.80 (b, 1H), 4.38 (m, 2H), 4.54 (m, 1H), 4.73 (dd, 1.8 Hz, 9.8Hz), 5.02 (b, 1H), 7.48 (s, 4H), 7.64 (s, 8H); ¹³C NMR (90 MHz, CD₂Cl₂)δ23.7, 24.0, 25.5, 26.0, 25.5, 27.3 (d, ²J_(CP)=3.4 Hz), 29.4, 31.5 (d,J_(CP)=25.5 Hz), 34.0, 34.8, 35.7, 37.2 (d, J_(CP)=30.3 Hz), 37.7, 56.5,65.2, 71.1, 75.2, 86.0 (d, 16.5 Hz), 96.0 (d, 8.1 Hz), 111.8 (t), 120.7,123.7, 126.7, 129.4 (dd, 28.5 Hz, 62.7 Hz), 135.4 (t), 162.3 (q, 49.4Hz), 188.4 (d, ²J_(CP)=17.9 Hz); ³¹P NMR (145 MHz, CD₂Cl₂) δ42.4;ESI+MS: 570 (cation+1); HRMS calculated for IrC₂₃H₄₁NOP 570.2477 found570.2437; HRMS calculated for C₃₂H₁₂F₂₄B 863.0649 found 863.0633.

[0162] 6c: ¹H NMR (360 MHz, CD₂Cl₂) δ1.09 (d, ³J_(HP)=15.5 Hz, 9H), 1.25(m, 1H), 1.46 (m, 2H), 1.80-2.40 (m, 11H), 3.19 (m, 1H), 3.78 (m, 2H),4.00 (m, 1H), 4.46 (dd, 5.2 Hz, 9.2 Hz, 1H), 4.81 (m, 1H), 4.93 (dd, 9.4Hz, 10.0 Hz, 1H), 5.23 (m, 1H), 7.01 (m, 2H), 7.34 (m, 3H), 7.48 (s, 4H)6.65 (s, 8H); ¹³C NMR (100 MHz, CD₂Cl₂) δ23.1 (d, ²J_(CP)=26.5 Hz),27.3, 27.6, 28.0, 28.5, 30.9, 31.4, 33.0 (d, J_(CP)=23.6 Hz), 33.9,35.4, 37.1 (d, J_(CP)=29.9 Hz), 61.7, 62.6, 69.4, 81.3, 93.3 (d, 11.6Hz), 94.2 (d, 13.9 Hz), 118.3, 121.3, 124.0, 126.5, 126.7, 129.6 (dd,25.2 Hz, 67.1 Hz), 130.5 (m), 135.6, 139.2, 162.5 (q, 49.5 Hz), 191.3(d, ²J_(CP)=19.8 Hz); ³¹P NMR (145 MHz, CD₂Cl₂) δ53.7; ESI+MS: 590(cation+1); HRMS calculated for IrC₂₅H37NOP 590.2164 found 570.2120.

[0163] 6d: ¹H NMR (360 MHz, CD₂Cl₂) δ1.18 (d, ³J_(HP)=15.5 Hz, 9H), 1.64(m, 3H), 1.80-2.50 (m, 11H), 2.61 (dd, 9.8 Hz, 14.1 Hz, 1H), 3.06 (m,2H), 4.08 (m, 1H), 4.29 (m, 2H), 4.49 (t, 9.0 Hz, 1H), 4.69 (dd, 2.7 Hz,9.4 Hz), 4.98 (m, 1H), 5.12 (b, 1H), 7.20 (m, 2H), 7.35 (m, 3H), 7.57(s, 4H), 7.73 (s, 8H); ¹³C NMR (100 MHz, CD₂Cl₂) δ23.7 (d, ²J_(CP)=24.6Hz), 26.6, 27.0 (d, ²J_(CP)=3.7 Hz), 27.2, 30.0 (d, J_(CP)=15.4 Hz),32.1, 32.3 (d, 6.3 Hz), 33.4, 36.3 (d, 3.7 Hz), 36.7 (d, J_(CP)=30.1Hz), 41.4, 60.4, 64.0, 65.2, 76.6, 88.9 (d, 12.6 Hz), 94.3 (d, 10.3 Hz),117.8, 120.9, 123.6, 126.3, 128.3, 129.1 (m), 129.6, 134.5, 135.2, 162.0(q, 49.5 Hz), 190.1 (d, ²J_(CP)=19.2 Hz); ³¹P NMR (145 MHz, CD₂Cl₂)δ52.0; ESI+MS: 604 (cation+1); HRMS calculated for IrC₂₆H39NOP 604.2320found 604.2322.

[0164] 6e: ¹H NMR (360 MHz, CD₂Cl₂) δ0.93 (d, 6.5 Hz, 3H), 0.97 (d, 6.5Hz), 1.18 (d, ³J_(HP)=15.5 Hz, 9H), 1.39 (m, 2H), 1.60 (m, 4H),1.80-2.50 (m, 11H), 3.06 (d, 7.6 Hz), 3.98 (m, 2H), 4.21 (m, 1H), 4.56(m, 2H), 4.77 (m, 1H), 5.01 (m, 1H), 7.57 (s, 4H), 7.73 (s, 8H); ¹³C NMR(90 MHz, CD₂Cl₂) δ21.6, 23.8, 23.9 (d, ²J_(CP)=24.6 Hz), 25.8, 26.5,27.1 (d, ²J_(CP)=3.7 Hz), 27.4, 30.2, 32.3 (d, J_(CP)=24.1 Hz), 32.5,33.8, 36.4 (d, 3.8 Hz), 37.0 (d, J_(CP)=30.2 Hz), 45.0, 60.4, 63.3,64.0, 77.6, 89.2 (d, 12.4 Hz), 64.6 (d, 40.9 Hz), 118.1 (t), 120.7,123.7, 126.7, 129.5 (dd, 37.7 Hz, 76.2 Hz), 135.4 (t, 103.7 Hz), 162.4(q, 49.7 Hz), 189,5 (d, ²J_(CP)=24.6 Hz); ³¹P NMR (145 MHz, CD₂Cl₂)δ51.3; ESI+MS: 570 (cation+1); HRMS calculated for IrC₂₃H₄₁NOP 570.2477found 570.2423.

[0165] 6f: ¹H NMR (400 MHz, CD₂Cl₂) δ0.79 (d, 6.8 Hz, 3H), 1.00 (d, 7.1Hz, 3H), 1.18 (d, ³J_(HP)=15.5 Hz, 9H), 1.80-2.30 (m, 12H), 2.40 (m,2H), 3.55 (m, 1H), 4.18 (m, 1H), 3.93 (m, 1H), 4.46 (m, 1H), 4.52 (t,9.4 Hz, 1H), 4.58 (m, 1H), 4.75 (dd, 3.6 Hz, 9.7 Hz, 1H), 5.02 (m, 1H),7.61 (s, 4H), 7.77 (s, 8H); ¹³C NMR (100 MHz, CD₂Cl₂) δ14.3 (d, 9.6 Hz),18.6 (d, 3.5 Hz), 22.6 (d, ²J_(CP)=29.7 Hz), 27.1 (d, ²J_(CP)=4.6 Hz),27.6, 27.7, 31.5, 31.8, 32.5, 33.5 (d, J_(CP)=21.2 Hz), 35.1, 36.4 (d,J_(CP)=30.4 Hz), 62.5 (d, 7.5 Hz), 65.4, 68.9, 73.3, 85.6 (d, 14.2 Hz),94.9 (d, 8.7 Hz), 117.7, 120.9, 123.6, 126.3, 129.2 (dd, 37.2 Hz, 68.5Hz), 135.2, 162.1 (q, 49.7 Hz), 187.0 (d, ²J_(CP)=20.9 Hz); ³¹P NMR (145MHz, CD₂Cl₂) δ60.0; ESI+MS: 556 (cation+1); ESI-MS: 863 (anion); HRMScalculated for IrC₂₂H₃₉NOP 556.2320 found 556.2309; HRMS calculated forC₃₂H₁₂F₂₄B 863.0649 found 863.0650.

EXAMPLE 10 Asymmetric Reduction of Unfunctionalized Alkenes GeneralHydrogenation Procedure

[0166] To a solution of an olefin substrate (0.2 mmol) in CH₂Cl₂ (2 mL)was added Ir complex 6 (2 μmol, 1 mol %) under nitrogen. The solutionwas then transferred into an autoclave. The hydrogenation was performedat room temperature under 50 bar of H₂ for 12-48 h. After carefullyreleasing the hydrogen, the reaction mixture was evaporated. The residuewas re-dissolved with ethyl acetate, which was subsequently passedthrough a short silica gel plug to remove the catalyst.

[0167] The resulting solution was directly used for chiral GC or HPLC tomeasure the enantiomeric excess.

[0168] Ir-catalyzed Asymmetric Hydrogenation of Methylstilbenes

Entry^([a]) Substrate R Catalyst ee %^([b]) Config.^([c]) 1 H 6a 91 R 2H 6b 81 R 3 H 6c 95 R 4 H 6d 89 R 5 H 6e 75 R 6 H 6f 77 S 7 OMe 6c 91 R8 Cl 6c 90 R

[0169] Ir-catalyzed Asymmetric Hydrogenation of β-methylcinnamic esters

Entry^([a]) Substrate R Catalyst ee %^([b]) Config.^([c]) 1 7 Ph 6a 94 R2 7 Ph 6b 91 R 3 7 Ph 6c 98 R 4 7 Ph 6d 92 R 5 7 Ph 6e 95 R 6 7 Ph 6f 93S 7 8 p-F—Ph 6c 95 R 8 9 p-Cl—Ph 6c 98 R 9 10 p-CH₃—Ph 6c 97 R 10 11p-OCF₃—Ph 6c 97 R 11 12 p-OCH₃—Ph 6c 97 R 12 13 m-CH₃—Ph 6c 99 R 13 141-naphthyl 6c 98 R 14 15 2-naphthyl 6c 95 R 15 (Z)-9 p-Cl—Ph 6c 80 S

[0170] A series of (E)-α,β-unsaturated esters were prepared via a Heckreaction according to a known procedure: Littke, A. F.; Fu, G. C. J. Am.Chem. Soc., 2001, 123, 6989-7000. To a Schlenk flask was added arylhalide (6.6 mmol), methyl crotonate (1.40 mL, 13.2 mmol), Pd₂(dba)₂ (151mg, 165 μmol), Cy₂NMe (1.55 mL, 7.26 mmol), degassed dried dioxane (20mL), and then ^(t)Bu₃P (67 mg, 0.33 mmol). The whole mixture was stirredunder N₂ at rt overnight. At the conclusion of the reaction, the mixturewas diluted with Et₂O, filtered through a pad of silica gel with copiouswashing, concentrated, and purified through column chromatography togive product in 70-80% yield.

[0171] 7: ¹H NMR (300 MHz, CDCl₃) δ2.62 (d, 1.3 Hz, 3H), 3.78 (s, 3H),6.17 (d, 1.2 Hz, 1H), 7.40 (m, 3H), 7.51 (m, 2H); ¹³C NMR (90 MHz,CDCl₃) δ18.4, 51.5, 117.1, 126.7, 128.9, 129.5, 142.6, 156.3, 167.7;APCI MS: 177 (M⁺+1); HRMS calculated for C₁₁H₁₃O₂ 177.0916 found177.0906.

[0172] 8: ¹H NMR (360 MHz, CDCl₃) δ2.55 (d, 1.2 Hz, 3H), 3.74 (s, 3H),6.09 (d, 1.2 Hz, 1H), 7.05 (m, 2H), 7.45 (m, 2H); ¹³C NMR (90 MHz,CDCl₃) δ18.2, 51.3, 115.6 (d, 21.6 Hz), 116.8, 128.8 (d, 32.0 Hz),138.4, 154.7, 162.1, 164.8, 167.3; APCI MS: 195 (M⁺+1); HRMS calculatedfor C₁₁H₁₂O₂F 195.0821 found 195.0824.

[0173] 9: ¹H NMR (300 MHz, CDCl₃) δ2.58 (d, 1.3 Hz, 3H), 3.78 (s, 3H),6.14 (dd, 1.2 Hz, 2.4 Hz, 1H), 7.38 (m, 4H); ¹³C NMR (75 MHz, CDCl₃)δ18.3, 51.6, 117.5, 128.0, 129.1, 135.5, 140.9, 154.8, 167.5; APCI MS:211 (M⁺+1); HRMS calculated for C₁₁H₁₂O₂Cl 211.0526 found 211.0519.

[0174] 10: ¹H NMR (300 MHz, CDCl₃) δ2.40 (s, 3H), 2.61 (d, 1.2 Hz, 3H),3.79 (s, 3H), 6.17 (d, 1.2 Hz, 1H), 7.21 (d, 8.0 Hz, 2H), 7.42 (d, 8.0Hz, 2H); ¹³C NMR (75 MHz, CDCl₃) δ18.3, 21.6, 51.5, 116.2, 126.7, 129.6,139.6, 156.2, 167.8; APCI MS: 191 (M³⁰ +1); HRMS calculated for C₁₂H₁₅O₂191.1072 found 191.1058.

[0175] 11: ¹H NMR (360 MHz, CDCl₃) δ2.59 (d, 1.2 Hz, 3H), 3.79 (s, 3H),6.15 (d, 1.2 Hz, 1H), 7.24 (d, 8.1 Hz, 2H), 2.55 (dd, 2.0 Hz, 7.9 Hz);¹³C NMR (90 MHz, CDCl₃) δ18.1, 51.3, 117.7, 119.2, 121.0, 121.1, 128.0,140.9, 149.9, 154.3, 167.1;

[0176] 12: ¹H NMR (300 MHz, CDCl₃) δ2.58 (d, 1.2 Hz, 3H), 3.74 (s, 3H),3.81 (s, 3H), 6.13 (dd, 1.1 Hz, 2.4 Hz, 1H), 6.89 (dd, 2.1 Hz, 6.8 Hz,2H), 7.45 (dd, 2.1 Hz, 6.8 Hz, 2H); ¹³C NMR (75 MHz, CDCl₃) δ18.0, 51.4,55.7, 114.2, 115.2, 134.5, 155.6, 160.9, 167.8; APCI MS: 207 (M³⁰ +1);HRMS calculated for C₁₂H₁₅O₃207.1021 found 207.1023.

[0177] 13: ¹H NMR (360 MHz, CDCl₃) δ2.40 (s, 3H), 2.60 (d, 1.0 Hz, 3H),3.78 (s, 3H), 6.16 (d, 1.0 Hz, 1H), 7.21 (m, 1H), 7.29 (m, 3H); ¹³C NMR(90 MHz, CDCl₃) δ18.2, 21.6, 51.2, 116.8, 123.6, 127.2, 128.6, 130.0,138.3, 142.4, 156.3, 167.5; ESI MS: 191 (M³⁰ +1); HRMS calculated forC₁₂H₁₅O₂ 191.1072 found 191.1091.

[0178] 14: ¹H NMR (360 MHz, CDCl₃) δ2.68 (s, 3H), 3.83 (s, 3H), 6.04 (s,1H), 7.32 (m, 1H), 7.53 (m, 3H), 7.90 (m, 3H); ¹³C NMR (90 MHz, CDCl₃)δ21.9, 51.3, 120.4, 124.4, 125.4, 126.2, 126.5, 128.4, 128.7, 130.3,133.9, 142.2, 157.6, 167.2; ESI MS: 227 (M³⁰ +1); HRMS calculated forC₁₅H₁₅O₂ 227.1072 found 227.1066.

[0179] 15: ¹H NMR (300 MHz, CDCl₃) δ2.74 (s, 3H), 3.82 (s, 3H), 6.33 (s,1H), 7.56 (m, 3H), 7.90 (m, 4H); ¹³C NMR (75 MHz, CDCl₃) δ18.4, 51.6;117.5, 124.4, 126.4, 127.0, 127.2, 128.0, 128.6, 128.9, 133.5, 133.9,139.6, 156.1, 167.7; APCI MS: 227 (M³⁰ +1); HRMS calculated for C₁₅H₁₅O₂227.1072 found 227.1064.

[0180] Analytical Data and GC or HPLC Conditions for New HydrogenationProducts

[0181] Hydrogenation Product of 7

[0182] 98% ee; [α]²⁰ _(D)=−15.5°(c=0.7, CHCl₃); chiral HPLC: ChiralcelOJH, hex: iPr=95:5, t_(R)=7.9 min (R), 9.0 min (S); ¹H NMR (300 MHz,CDCl₃) δ1.33 (d, 7.0 Hz, 3H), 2.58 (dd, 8.2 Hz, 15.1 Hz, 1H), 2.66 (dd,6.9 Hz, 15.1 Hz, 1H), 3.30 (s, 3H), 7.31 (m, 5H); ¹³C NMR (75 MHz,CDCl₃) δ22.2, 36.9, 43.2, 51.9, 126.8, 127.1, 128.9, 146.1, 173.3; APCIMS: 196 (M⁺+NH₄ ⁺); HRMS calculated for C₁₁H₁₈NO₂ 196.1338 found196.1335.

[0183] Hydrogenation Product of 8

[0184] 95% ee; [α]²⁰ _(D)=−1.9°(c=0.5, CHCl₃); chiral GC: Chiralselect1000, 140° C., t_(R)=19.3 min (S), 19.9 (R); ¹H NMR (400 MHz, CDCl₃)δ1.31 (d, 7.0 Hz, 3H), 2.60 (m, 2H), 3.30 (m, 1H), 3.64 (s, 3H), 7.16(d, 8.0 Hz, 2H), 7.27 (m, 2H); ¹³C NMR (100 MHz, CDCl₃) δ22.2, 36.2,43.0, 51.9, 121.4, 128.4, 144.7, 148.1, 172.9; APCI MS: 214 (M⁺+NH₄ ⁺);HRMS calculated for C₁₁H₁₇FNO₂ 214.1243 found 214.1248.

[0185] Hydrogenation Product of 9

[0186] 98% ee; [α]²⁰ _(D)=−32.4°(c=1.1, CHCl₃); chiral GC: Chiralselect1000, 140° C., t_(R)=53.7 min (S), 55.5 min (R); ¹H NMR (300 MHz, CDCl₃)δ1.29 (d, 7.0 Hz, 3H), 2.58 (m, 2H), 3.29 (m, 1H), 3.63 (s, 3H), 7.17(m, 2H), 7.27 (m, 2H); ¹³C NMR (75 MHz, CDCl₃) δ22.2, 36.3, 43.0, 52.0,128.5, 129.0, 132.4, 144.5, 173.0; APCI MS: 230 (M⁺+NH₄ ⁺); HRMScalculated for C₁₁H₁₇ClNO₂ 230.0948 found 230.0942.

[0187] Hydorgenation Product of 10

[0188] 97% ee; [α]²⁰ _(D)=−2.4°(c=0.3, CHCl₃); chiral GC: Chiralselect1000, 140° C., t_(R)=27.1 min (S), 27.7 min (R); ¹H NMR (400 MHz, CDCl₃)δ1.31 (d, 7.0 Hz, 3H), 2.35 (s,3H), 2.56 (dd, 8.2 Hz, 15.1 Hz, 1H), 2.64(dd, 7.0 Hz, 15.1 Hz, 1H), 3.29 (m, 1H), 3.66 (s, 3H), 7.14 (s, 4H); ¹³CNMR (100 MHz, CDCl₃) δ21.4, 22.3, 36.4, 43.2, 51.9, 127.0, 129.6, 136.3,143.1, 173.3; ESI MS: 210 (M⁺+NH₄ ⁺); HRMS calculated for C₁₂H₂₀NO₂210.1494 found 210.1479.

[0189] Hydrogenation Product of 11

[0190] 97% ee; [α]²⁰ _(D)=−23.4°(c=0.3, CHCl₃); chiral GC: Chiralselect1000, 140° C., t_(R)=20.0 min (S), 20.5 min (R); ¹H NMR (400 MHz, CDCl₃)δ1.30 (d, 7.0 Hz, 3H), 2.58 (m, 2H), 3.29 (m, 1H), 3.66 (s, 3H), 6.99(m, 2H), 7.20 (m, 2H); ¹³C NMR (100 MHz, CDCl₃) δ22.4, 36.2, 43.2, 51.9,115.5, 128.5, 141.7, 160.6, 163.1, 173.1; ESI MS: 280 (M⁺+NH₄ ⁺); HRMScalculated for C₁₂H₁₇F₃NO₃ 280.1161 found 280.1173.

[0191] Hydrogenation Product of 12

[0192] 97% ee; [α]²⁰ _(D)=−23.8°(c=0.7, CHCl₃); chiral HPLC: ChiralcelOJH, hex: iPr=95: 5, t_(R)=12.1 min (R), 13.9 min (S); ¹H NMR (360 MHz,CDCl₃) δ1.27 (d, 7.5 Hz, 3H), 2.52 (dd, 8.0 Hz, 15.0 Hz, 1H), 2.59 (dd,7.1 Hz, 15.0 Hz, 1H), 3.61 (s, 3H), 3.78 (s, 3H), 6.83 (m, 2H), 7.15 (m,2H); ¹³C NMR (90 MHz, CDCl₃) δ22.1, 35.9, 43.2, 51.6, 55.4, 114.1,127.8, 138.1, 158.3, 173.1; ESI MS: 226 (M⁺+NH₄ ⁺); HRMS calculated forC₁₂H₂₀NO₃ 226.1443 found 226.1425.

[0193] Hydrogenation Product of 13

[0194] 99% ee; [α]²⁰ _(D)=−20.2°(c=0.5, CHCl₃); chiral GC: Chiralselect1000, 140° C., t_(R)=47.0 min (S), 48.0 min (R); ¹H NMR (360 MHz, CDCl₃)δ1.31 (d, 7.0 Hz, 3H), 2.35 (s, 3H), 2.52 (dd, 8.4 Hz, 15.2 Hz, 1H),2.64 (dd, 6.7 Hz, 15.1 Hz, 1H), 3.25 (m, 1H), 3.65 (s, 3H), 7.04 (m,3H), 7.21 (m, 1H); ¹³C NMR (90 MHz, CDCl₃) δ21.6, 22.0, 35.5, 36.5,42.9, 51.6, 123.9, 127.4, 127.7, 128.6, 138.2, 145.9, 173.1; ESI MS: 210(M⁺+NH₄ ⁺); HRMS calculated for C₁₂H₂₀NO₂ 210.1494 found 210.1479.

[0195] Hydrogenation Product of 14

[0196] 98% ee; [α]²⁰ _(D)=+1.8°(c=0.72, CHCl₃); chiral HPLC: ChiralcelOJH, hex: iPr=99:1, t_(R)=32.2 min (R), 36.5 min (S); ¹H NMR (400 MHz,CDCl₃) δ1.48 (d, 6.9 Hz, 3H), 2.67 ( dd, 9.3 Hz, 15.3 Hz, 1H), 2.89 (dd,5.3 Hz, 15.3 Hz, 1H), 3.70 (s, 3H), 4.21 (m, 1H), 7.50 (m, 4H), 7.77 (d,8.0 Hz, 1H), 7.90 (d, 8.0 Hz, 1H), 8.22 (d, 8.4 Hz, 1H); ¹³C NMR (100MHz, CDCl₃) δ21.6, 31.2, 42.7, 51.9, 122.7, 123.4, 125.9, 126.5, 127.4,129.4, 131.5, 134.4, 142.1, 173.5; ESI MS: 246 (M⁺+NH₄ ⁺); HRMScalculated for C₁₅H₂₀NO₂ 246.1494 found 246.1497.

[0197] Hydrogenation Product of 15

[0198] 95% ee; [α]²⁰ _(D)=−40.2°(c=1.2, CHCl₃); chiral HPLC: ChiralcelOJH, hex: iPr=99:1, t_(R)=65.2 min (R), 70.9 min (S); ¹H NMR (300 MHz,CDCl₃) δ1.43 (d, 7.0 Hz, 3H), 2.68 (dd, 8.1 Hz, 15.2 Hz, 1H), 2.78 (dd,7.0 Hz, 15.2 Hz, 1H), 3.49 (m, 1H), 3.65 (s, 3H), 7.46 (m, 3H), 7.69 (s,1H), 7.83 (m, 2H); ¹³C NMR (75 MHz, CDCl₃) δ22.2, 37.0, 43.1, 52.0,125.4, 125.8, 125.9, 126.4, 128.0, 128.1, 128.6, 132.8, 134.0, 143.6,173.3; ESI MS: 246 (M⁺+NH₄ ⁺); HRMS calculated for C₁₅H₂₀NO₂ 246.1494found 246.1481.

EXAMPLE 10 Synthesis and Structure of the following Bisphosphine

[0199] Synthesis and application of TangPhos type ligands

[0200] A chiral bisphosphine with the following structure was preparedby the procedure outlined above:

[0201] The X-ray structure of the corresponding bisphosphine sulfide wasobtained and is shown below:

[0202] Further Applications

[0203] Rh-compound with this ligand is an effective catalyst forhydrogenation of enamides (e.g., E/Z mixture of PhCH(NHAc)CHCOOEt) tomake beta amino acids (up to 99% ee has been achieved).

[0204] The present invention has been described with particularreference to the preferred embodiments. It should be understood that theforegoing descriptions and examples are only illustrative of theinvention. Various alternatives and modifications thereof can be devisedby those skilled in the art without departing from the spirit and scopeof the present invention. Accordingly, the present invention is intendedto embrace all such alternatives, modifications, and variations thatfall within the scope of the appended claims.

What is claimed is:
 1. A chiral ligand represented by the followingformula or its enantiomer:

wherein X is a divalent group selected from the group consisting of:(CR⁴R⁵)_(n), (CR⁴R⁵)_(n)-Z-(CR⁴R⁵)_(n) and group represented by theformula:

wherein each n is independently an integer from 1 to 6; wherein each R⁴and R⁵ is independently selected from the group consisting of: hydrogen,alkyl, aryl, substituted alkyl, substituted aryl, hetereoaryl,ferrocenyl, halogen, hydroxy, alkoxy, aryloxy, alkylthio, arylthio andamido; and wherein Z is selected from the group consisting of: O, S,—COO—, —CO—, O—(CR⁴R⁵)_(n)—O, CH₂ (C₆H₄), CH₂ (Ar), CH₂(hetereoaryl),alkenyl, CH₂(alkenyl), C₅H₃N, divalent aryl,2,2′-divalent-1,1′-biphenyl, SiR′₂, PR′ and NR⁶ wherein each of R′ andR⁶ is independently selected from the group consisting of: hydrogen,alkyl, substituted alkyl, aryl, substituted aryl, hydroxy, alkoxy,aryloxy, acyl and alkoxycarbonyl; wherein R is selected from the groupconsisting of: alkyl, aryl, substituted alkyl, substituted aryl,hetereoaryl, ferrocenyl, alkoxy and aryloxy; wherein E is selected fromthe group consisting of: PR′₂, PR′R″, o-substituted pyridine, oxazoline,chiral oxazoline, CH₂(chiral oxazoline), CR′2(chiral oxazoline),CH₂PR′₂, CH₂(o-substituted pyridine), SiR′₃, CR′₂OH and a grouprepresented by the formula:

wherein Y is selected from the group consisting of: (CR⁴R⁵)_(m) and(CR⁴R⁵)_(m)-Z-(CR⁴R⁵)_(m); wherein each m is independently an integerfrom 0 to 3; wherein each R⁴ and R⁵ is independently selected from thegroup consisting of: hydrogen, alkyl, aryl, substituted alkyl,substituted aryl, hetereoaryl, ferrocenyl, halogen, hydroxy, alkoxy,aryloxy, alkylthio, arylthio and amido; and wherein Z is selected fromthe group consisting of: O, S, —CO—, —COO—, O—(CR⁴R⁵)_(n)—O, CH₂ (C₆H₄),CH₂ (Ar), CH₂(hetereoaryl), alkenyl, CH₂(alkenyl), C₅H₃N, divalent aryl,2,2′-divalent-1,1′-biphenyl, SiR′₂, PR′ and NR⁶ wherein each of R′ andR⁶ is independently selected from the group consisting of: hydrogen,alkyl, substituted alkyl, aryl, substituted aryl, hydroxy, alkoxy,aryloxy, acyl and alkoxycarbonyl.
 2. The chiral ligand of claim 1,wherein: X is selected from the group consisting of: (CH₂)_(n) wherein nis from 1 to 6, CH₂OCH₂, CH₂NHCH₂, CH₂CH(R′)CH(R′), CH₂CH(OR′)CH(OR′),CH₂CH(OH)CH(OH), CH₂NR′CH₂, CH₂CH₂NR′CH₂, CH₂CH₂OCH₂ and a grouprepresented by the formula:

wherein each R⁴ and R⁵ is independently selected from the groupconsisting of: hydrogen, alkyl, aryl, substituted alkyl and substitutedaryl.
 3. The chiral ligand of claim 1, wherein: Y is selected from thegroup consisting of: (CH₂)_(n) wherein n is from 0 to 3, CH₂NHCH₂,CH₂SCH₂, CH₂PR′CH₂, CR′2, CO, SiR′₂, C₅H₃N, C₆H₄, alkylene, substitutedalkylene, 1,2-divalent arylene, 2,2′-divalent-1,1′-biphenyl, substitutedaryl, hetereoaryl and ferrocene.
 4. The chiral ligand of claim 1,wherein the ligand is in the form of a phosphine borane, phosphinesulfide or phosphine oxide.
 5. A chiral ligand represented by theformula and its enantiomer:

wherein R is selected from the group consisting of: alkyl, aryl,substituted alkyl, substituted aryl, hetereoaryl, ferrocenyl, alkoxy andaryloxy; and wherein n is from 0 to
 2. 6. The chiral ligand of claim 5,wherein n is 0, 1 or 2, and R is selected from the group consisting of:CH₃, Et, iPr, t-Bu, 1-adamantyl, Et₃C, cyclo-C₅H₉, cyclo-C₆H₁₁, phenyl,p-tolyl, 3,5-dimethylphenyl, 3,5-di-t-butyl phenyl, ortho-anisyl andnaphthyl.
 7. The chiral ligand of claim 5, wherein the ligand is in theform of a phosphine borane, phosphine sulfide or phosphine oxide.
 8. Achiral ligand represented by the formula and its enantiomer:


9. A chiral ligand represented by the formula and its enantiomer:


10. A chiral ligand selected from the group consisting of compoundsrepresented by formulas L1 through L52 and their enantiomers:


11. A catalyst prepared by a process comprising: contacting a transitionmetal salt, or a complex thereof, and a chiral ligand selected from thegroup consisting of compounds represented by the formula or itsenantiomer:

wherein X is a divalent group selected from the group consisting of:(CR⁴R⁵)_(n), (CR⁴R⁵)_(n)-Z-(CR⁴R⁵)_(n) and group represented by theformula:

wherein each n is independently an integer from 1 to 6; wherein each R⁴and R⁵ is independently selected from the group consisting of: hydrogen,alkyl, aryl, substituted alkyl, substituted aryl, hetereoaryl,ferrocenyl, halogen, hydroxy, alkoxy, aryloxy, alkylthio, arylthio andamido; and wherein Z is selected from the group consisting of: O, S,—COO—, —CO—, O—(CR⁴R⁵)_(n)—O, CH₂ (C₆H₄), CH₂ (Ar), CH₂(hetereoaryl),alkenyl, CH₂(alkenyl), C₅H₃N, divalent aryl,2,2′-divalent-1,1′-biphenyl, SiR′₂, PR′ and NR⁶ wherein each of R′ andR⁶ is independently selected from the group consisting of: hydrogen,alkyl, substituted alkyl, aryl, substituted aryl, hydroxy, alkoxy,aryloxy, acyl and alkoxycarbonyl; wherein R is selected from the groupconsisting of: alkyl, aryl, substituted alkyl, substituted aryl,hetereoaryl, ferrocenyl, alkoxy and aryloxy; wherein E is selected fromthe group consisting of: PR′₂, PR′R″, o-substituted pyridine, oxazoline,chiral oxazoline, CH₂(chiral oxazoline), CR′2(chiral oxazoline),CH₂PR′₂, CH₂(o-substituted pyridine), SiR′₃, CR′₂OH and a grouprepresented by the formula:

wherein Y is selected from the group consisting of: (CR⁴R⁵)_(m) and(CR⁴R⁵)_(m)-Z-(CR⁴R⁵)_(m); wherein each m is independently an integerfrom 0 to 3; wherein each R⁴ and R⁵ is independently selected from thegroup consisting of: hydrogen, alkyl, aryl, substituted alkyl,substituted aryl, hetereoaryl, ferrocenyl, halogen, hydroxy, alkoxy,aryloxy, alkylthio, arylthio and amido; and wherein Z is selected fromthe group consisting of: O, S, —CO—, —COO—, O—(CR⁴R⁵)_(n)—O, CH₂ (C₆H₄),CH₂ (Ar), CH₂(hetereoaryl), alkenyl, CH₂(alkenyl), C₅H₃N, divalent aryl,2,2′-divalent-1,1′-biphenyl, SiR′₂, PR′ and NR⁶ wherein each of R′ andR⁶ is independently selected from the group consisting of: hydrogen,alkyl, substituted alkyl, aryl, substituted aryl, hydroxy, alkoxy,aryloxy, acyl and alkoxycarbonyl.
 12. The catalyst of claim 11, whereinsaid catalyst is a racemic mixture of enantiomers.
 13. The catalyst ofclaim 11, wherein said catalyst is a non-racemic mixture of enantiomers.14. The catalyst of claim 31, wherein said catalyst is one of theenantiomers.
 15. The catalyst of claim 11, wherein said transition metalis selected from the group consisting of: Ag, Pt, Pd. Rh, Ru, Ir, Cu,Ni, Mo, Ti, V, Re and Mn.
 16. The catalyst of claim 15, wherein saidtransition metal is selected from the group consisting of: Cu, Ag, Ni,Pt, Pd, Rh, Ru and Ir.
 17. The catalyst of claim 11, wherein saidtransition metal salt, or complex thereof, is selected from the groupconsisting of: AgX; Ag(OTf); Ag(OTf₂; AgOAc; PtCl₂; H₂PtCl₄; Pd₂(DBA)₃;Pd(OAc)₂; PdCl₂(RCN)₂; (Pd(allyl)Cl)₂; Pd(PR₃)₄; (Rh(NBD)₂)X; (Rh(NBD)Cl)₂; (Rh(COD)Cl)₂; (Rh(COD)₂)X; Rh(acac)(CO)₂;Rh(ethylene)₂(acac); (Rh(ethylene)₂Cl)₂; RhCl(PPh₃)₃; Rh(CO)₂Cl₂;RuHX(L)₂(diphosphine), RuX₂(L)₂ (diphosphine), Ru(arene)X₂(diphosphine),Ru(aryl group)X₂; Ru(RCOO)₂(diphosphine); Ru(methallyl)2(diphosphine);Ru(aryl group)X₂(PPh₃)₃; Ru(COD)(COT); Ru(COD)(COT)X; RuX₂(cymen);Ru(COD)_(n); Ru(aryl group)X₂(diphosphine); RuCl₂(COD); (Ru(COD)₂)X;RuX₂(diphosphine); RuCl₂(═CHR)(PR′₃)₂; Ru(ArH)Cl₂; Ru(COD)(methallyl)₂;(Ir (NBD)₂Cl)₂; (Ir(NBD)₂)X; (Ir(COD)₂Cl)₂; (Ir(COD)₂)X; CuX (NCCH₃)₄;Cu(OTf; Cu(OTf₂; Cu(Ar)X; CuX; Ni(acac)₂; NiX₂; (Ni(allyl)X)₂; Ni(COD)₂;MoO₂(acac)₂; Ti(OiPr)₄; VO(acac)₂; MeReO₃; MnX₂ and Mn(acac)₂; whereineach R and R′ is independently selected from the group consisting of:alkyl or aryl; Ar is an aryl group; and X is a counteranion.
 18. Thecatalyst of claim 17, wherein L is a solvent and wherein saidcounteranion X is selected from the group consisting of: halogen, BF₄,B(Ar)₄ wherein Ar is fluorophenyl or 3,5-di-trifluoromethyl-1-phenyl,ClO₄, SbF₆, PF₆, CF₃SO₃, RCOO and a mixture thereof.
 19. The catalyst ofclaim 11, prepared in situ or as an isolated compound.
 20. A process forpreparation of an asymmetric compound comprising: contacting a substratecapable of forming an asymmetric product by an asymmetric reaction and acatalyst prepared by a process comprising: contacting a transition metalsalt, or a complex thereof, and a chiral ligand selected from the groupconsisting of compounds represented by the formula or its enantiomer:

wherein X is a divalent group selected from the group consisting of:(CR⁴R⁵)_(n), (CR⁴R⁵)_(n)-Z-(CR⁴R⁵)_(n) and group represented by theformula:

wherein each n is independently an integer from 1 to 6; wherein each R⁴and R⁵ is independently selected from the group consisting of: hydrogen,alkyl, aryl, substituted alkyl, substituted aryl, hetereoaryl,ferrocenyl, halogen, hydroxy, alkoxy, aryloxy, alkylthio, arylthio andamido; and wherein Z is selected from the group consisting of: O, S,—COO—, —CO—, O—(CR⁴R⁵)_(n)—O, CH₂ (C₆H₄), CH₂ (Ar), CH₂(hetereoaryl),alkenyl, CH₂(alkenyl), C₅H₃N, divalent aryl,2,2′-divalent-1,1′-biphenyl, SiR′₂, PR′ and NR⁶ wherein each of R′ andR⁶ is independently selected from the group consisting of: hydrogen,alkyl, substituted alkyl, aryl, substituted aryl, hydroxy, alkoxy,aryloxy, acyl and alkoxycarbonyl; wherein R is selected from the groupconsisting of: alkyl, aryl, substituted alkyl, substituted aryl,hetereoaryl, ferrocenyl, alkoxy and aryloxy; wherein E is selected fromthe group consisting of: PR′₂, PR′R″, o-substituted pyridine, oxazoline,chiral oxazoline, CH₂(chiral oxazoline), CR′₂(chiral oxazoline),CH₂PR′₂, CH₂(o-substituted pyridine), SiR′₃, CR′₂OH and a-grouprepresented by the formula:

wherein Y is selected from the group consisting of: (CR⁴R⁵)_(m) and(CR⁴R⁵)_(m)-Z-(CR⁴R⁵)_(m); wherein each m is independently an integerfrom 0 to 3; wherein each R⁴ and R⁵ is independently selected from thegroup consisting of: hydrogen, alkyl, aryl, substituted alkyl,substituted aryl, hetereoaryl, ferrocenyl, halogen, hydroxy, alkoxy,aryloxy, alkylthio, arylthio and amido; and wherein Z is selected fromthe group consisting of: O, S, —CO—, —COO—, O—(CR⁴R⁵)_(n)—O, CH₂ (C₆H₄),CH₂ (Ar), CH₂(hetereoaryl), alkenyl, CH₂(alkenyl), C₅H₃N, divalent aryl,2,2′-divalent-1,1′-biphenyl, SiR′₂, PR′ and NR⁶ wherein each of R′ andR⁶ is independently selected from the group consisting of: hydrogen,alkyl, substituted alkyl, aryl, substituted aryl, hydroxy, alkoxy,aryloxy, acyl and alkoxycarbonyl.
 21. The process of claim 20, whereinsaid asymmetric reaction is selected from the group consisting of:hydrogenation, hydride transfer, allylic alkylation, hydrosilylation,hydroboration, hydrovinylation, hydroformylation, olefin metathesis,hydrocarboxylation, isomerization, cyclopropanation, Diels-Alderreaction, Heck reaction, isomerization, Aldol reaction, Michaeladdition; epoxidation, kinetic resolution and [m+n] cycloadditionwherein m=3 to 6 and n=2.
 22. The process of claim 21, wherein saidasymmetric reaction is hydrogenation and said substrate is selected fromthe group consisting of: imine, ketone, ethylenically unsaturatedcompound, enamine, enamide and vinyl ester.
 23. The process of claim 21,wherein said asymmetric reaction is an iridium, ruthenium, rhenium orpalladium-catalyzed hydrogenation of an olefin, imine, enamide orketone.
 24. A process for preparing (1R, 1R′, 2R, 2R′)-1,1′-di-alkyl-[2,2′]-diphospholanyl-1,1′-disulfide comprising the steps of:asymmetrically deprotonating a 1-alkyl-phospholane-1-sulfide withn-butyllithium/(−)-sparteine in a solvent to produce an anion of said1-alkyl-phospholane-1-sulfide; and contacting said anion of said1-alkyl-phospholane-1-sulfide and CuCl₂ to oxidatively couple said anionof said 1-alkyl-phospholane-1-sulfide and produce a reaction mixturecomprising said (1R, 1R′, 2R,2R′)-1,1′-di-alkyl-[2,2′]-diphospholanyl-1,1′-disulfide.
 25. The processof claim 24, wherein said alkyl is tert-butyl.
 26. The process of claim24, further comprising the step of: recrystallizing said (1R, 1R′, 2R,2R′)-1,1′-di-alkyl-[2,2′]-diphospholanyl-1,1′-disulfide from saidreaction mixture.
 27. The process of claim 26, further comprising thestep of: contacting said (1R, 1R′, 2R,2R′)-1,1′-di-alkyl-[2,2′]-diphospholanyl-1,1′-disulfide andhexachlorodisilane in a solvent to produce (1S, 1S′, 2R,2R′)-1,1′-di-alkyl-[2,2′]-diphospholanyl.
 28. A process for preparing(1S, 1S′, 2R, 2R′)-1,1′-di-alkyl-[2,2′]-diphospholanyl comprising thesteps of: asymmetrically deprotonating a 1-alkyl-phospholane-1-sulfidewith n-butyllithium/(−)-sparteine in a solvent to produce an anion ofsaid 1-alkyl-phospholane-1-sulfide; contacting said anion of said1-alkyl-phospholane-1-sulfide and CuCl₂ to oxidatively couple said anionof said 1-alkyl-phospholane-1-sulfide and produce a reaction mixturecomprising (1R, 1R′, 2R,2R′)-1,1′-di-alkyl-[2,2′]-diphospholanyl-1,1′-disulfide; recrystallizingsaid (1R, 1R′, 2R,2R′)-1,1′-di-alkyl-[2,2′]-diphospholanyl-1,1′-disulfide from saidreaction mixture; and contacting said (1R, 1R′, 2R,2R′)-1,1′-di-alkyl-[2,2′]-diphospholanyl-1,1′-disulfide andhexachlorodisilane in a solvent to produce (1S, 1S′, 2R,2R′)-1,1′-di-alkyl-[2,2′]-diphospholanyl.
 29. The process of claim 28,wherein said alkyl is tert-butyl.